Behavioral evidence of the functional interaction between the main and accessory olfactory system suggests a large olfactory system with a high plastic capability.

Olfaction is fundamental in many species of mammals. In rodents, the integrity of this system is required for the expression of parental and sexual behavior, mate recognition, identification of predators, and finding food. Different anatomical and physiological evidence initially indicated the existence of two anatomically distinct chemosensory systems: The main olfactory system (MOS) and the accessory olfactory system (AOS). It was originally conceived that the MOS detected volatile odorants related to food, giving the animal information about the environment. The AOS, on the other hand, detected non-volatile sexually relevant olfactory cues that influence reproductive behaviors and neuroendocrine functions such as intermale aggression, sexual preference, maternal aggression, pregnancy block (Bruce effect), puberty acceleration (Vandenbergh effect), induction of estrous (Whitten effect) and sexual behavior. Over the last decade, several lines of evidence have demonstrated that although these systems could be anatomically separated, there are neuronal areas in which they are interconnected. Moreover, it is now clear that both the MOS and the AOS process both volatile and no-volatile odorants, indicating that they are also functionally interconnected. In the first part of the review, we will describe the behavioral evidence. In the second part, we will summarize data from our laboratory and other research groups demonstrating that sexual behavior in male and female rodents induces the formation of new neurons that reach the main and accessory olfactory bulbs from the subventricular zone. Three factors are essential for the neurons to reach the AOS and the MOS: The stimulation frequency, the stimulus's temporal presentation, and the release of opioids induced by sexual behavior. We propose that the AOS and the MOS are part of a large olfactory system with a high plastic capability, which favors the adaptation of species to different environmental signals.

Increased proliferation and neuronal fate in prairie vole brain progenitor cells cultured in vitro: effects by social exposure and sexual dimorphism.

BACKGROUND: The prairie vole (Microtus ochrogaster) is a socially monogamous rodent that establishes an enduring pair bond after cohabitation, with (6 h) or without (24 h) mating. Previously, we reported that social interaction and mating increased cell proliferation and differentiation to neuronal fate in neurogenic niches in male voles. We hypothesized that neurogenesis may be a neural plasticity mechanism involved in mating-induced pair bond formation. Here, we evaluated the differentiation potential of neural progenitor cells (NPCs) isolated from the subventricular zone (SVZ) of both female and male adult voles as a function of sociosexual experience. Animals were assigned to one of the following groups: (1) control (Co), sexually naive female and male voles that had no contact with another vole of the opposite sex; (2) social exposure (SE), males and females exposed to olfactory, auditory, and visual stimuli from a vole of the opposite sex, but without physical contact; and (3) social cohabitation with mating (SCM), male and female voles copulating to induce pair bonding formation. Subsequently, the NPCs were isolated from the SVZ, maintained, and supplemented with growth factors to form neurospheres in vitro. RESULTS: Notably, we detected in SE and SCM voles, a higher proliferation of neurosphere-derived Nestin + cells, as well as an increase in mature neurons (MAP2 +) and a decrease in glial (GFAP +) differentiated cells with some sex differences. These data suggest that when voles are exposed to sociosexual experiences that induce pair bonding, undifferentiated cells of the SVZ acquire a commitment to a neuronal lineage, and the determined potential of the neurosphere is conserved despite adaptations under in vitro conditions. Finally, we repeated the culture to obtain neurospheres under treatments with different hormones and factors (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone); the ability of SVZ-isolated cells to generate neurospheres and differentiate in vitro into neurons or glial lineages in response to hormones or factors is also dependent on sex and sociosexual context. CONCLUSION: Social interactions that promote pair bonding in voles change the properties of cells isolated from the SVZ. Thus, SE or SCM induces a bias in the differentiation potential in both sexes, while SE is sufficient to promote proliferation in SVZ-isolated cells from male brains. In females, proliferation increases when mating is performed. The next question is whether the rise in proliferation and neurogenesis of cells from the SVZ are plastic processes essential for establishing, enhancing, maintaining, or accelerating pair bond formation. Highlights 1. Sociosexual experiences that promote pair bonding (social exposure and social cohabitation with mating) induce changes in the properties of neural stem/progenitor cells isolated from the SVZ in adult prairie voles. 2. Social interactions lead to increased proliferation and induce a bias in the differentiation potential of SVZ-isolated cells in both male and female voles. 3. The differentiation potential of SVZ-isolated cells is conserved under in vitro conditions, suggesting a commitment to a neuronal lineage under a sociosexual context. 4. Hormonal and growth factors treatments (brain-derived neurotrophic factor, estradiol, prolactin, oxytocin, and progesterone) affect the generation and differentiation of neurospheres, with dependencies on sex and sociosexual context. 5. Proliferation and neurogenesis in the SVZ may play a crucial role in establishing, enhancing, maintaining, or accelerating pair bond formation.

In this study, researchers evaluated whether social interactions and copulation induce changes in the proliferation and differentiation of neural progenitor cells in adult male and female voles using an in vitro neurosphere formation assay. The following groups were assigned: control animals without any exposure to another vole outside their litter, another group with social exposure consisting of sensory exposure to a vole of the opposite sex and a third group with social cohabitation and copulation. Forty eight hours after social interactions, cells were isolated from the neurogenic niche subventricular zone (SVZ) and cultured to assess their self-renewal and proliferation abilities to form neurospheres. The results showed in the social interaction groups, a greater number and growth of neurospheres in both males and females. Differentiation capacity was assessed by immunodetection of MAP2 and GFAP to identify neurons or glia, respectively, arise from neurospheres, with an increase in neuronal fate in groups with social interaction. In the second part of the study, the researchers analyzed the effect of different hormone and growth factor treatments and found that the response in both proliferation and differentiation potential may vary depending on the sociosexual context or sex. This study suggests that social interactions leading to pair bond formation alter the properties of SVZ cells, whereby proliferation and neurogenesis may have an impact on the establishment and maintenance of pair bonding.

Being friendly: paced mating for the study of physiological, behavioral, and neuroplastic changes induced by sexual behavior in females.

Paced mating in rats is an experimental condition that allows the evaluation of sexual behavior in a way that closely resembles what occurs in seminatural and natural conditions enabling the female to control the rate of the sexual interaction. In conventional non-paced mating tests, females cannot escape from male approaches, which may lead to an unrewarding overstimulation. Paced mating is an alternative laboratory procedure that improves animal welfare and has a higher ethological relevance. The use of this procedure contributed to the identification of physiological and behavioral factors that favor reproduction. Paced mating includes motivational and behavioral components differentiating quantitative and qualitative characteristics that are critical for the induction of the rewarding properties of mating. These positive consequences ensure that the behavior will be repeated, favoring the species' survival. Sexual reward is an immediate consequence of paced mating, mediated mainly by the endogenous opioid system. Paced mating also induces long-lasting neuroplastic changes, including gene expression, synthesis of proteins, and neurogenesis in sex-relevant brain areas. The interest in paced mating is growing since the complexity of its elements and consequences at different levels in a laboratory setting resembles what occurs in natural conditions. In this review, we analyze the classic studies and recent publications demonstrating the advantages of using paced mating to evaluate different aspects of sexual behavior in females.

Immediate Results after Multiple Arterial Grafts in Coronary Artery Bypass Graft Surgery in the São Paulo State: Cross Cohort Study. / Resultados Imediatos após Múltiplos Enxertos Arteriais em Cirurgia de Revascularização Miocárdica no Estado de São Paulo: Estudo de Coorte.

BACKGROUND: The short-term results after using arterial grafts still raise questions and doubts for medical society. OBJECTIVE: To compare the immediate outcomes of patients undergoing single arterial graft versus multiple arterial grafts coronary artery bypass grafting surgery. METHODS: Cross-sectional cohort study in the São Paulo Registry of Cardiovascular Surgery II (REPLICCAR II). Perioperative data from 3122 patients were grouped by the number of arterial grafts used, and their outcomes were compared: reoperation, deep sternal wound infection (DSWI), stroke, acute kidney injury, prolonged intubation (>24 hours), short hospital stay (<6 days), prolonged hospital stay (>14 days), morbidity and mortality. Propensity Score Matching (PSM) matched 1062 patients, adjusted for the mortality risk. RESULTS: After PSM, the single arterial graft group showed patients with advanced age, more former smokers, hypertension, diabetes, stable angina, and previous myocardial infarction. In the multiple arterial grafts, there was a predominance of males, recent pneumonia, and urgent surgeries. After the procedure, there was a higher incidence of pleural effusion (p=0.042), pneumonia (p=0.01), reintubation (p=0.006), DSWI (p=0.007), and sternal debridement (p=0.015) in the multiple arterial grafts group, however, less need for blood transfusion (p=0.005), extremity infections (p=0.002) and shorter hospital stays (p=0.036). Bilateral use of the internal thoracic artery was not related to increased DSWI rate, but glycosylated hemoglobin >6.40% (p=0.048). CONCLUSION: Patients undergoing the multiarterial technique had a higher incidence of pulmonary complications, and DSWI, where glycosylated hemoglobin ≥6.40%, had a greater influence on the infectious outcome than the choice of grafts.

FUNDAMENTO: Os resultados a curto prazo após o uso de enxertos arteriais ainda suscitam questionamentos e dúvidas na sociedade médica. OBJETIVO: Comparar os resultados imediatos de pacientes submetidos à cirurgia de revascularização do miocárdio com enxerto arterial único versus enxertos arteriais múltiplos. MÉTODOS: Estudo de coorte transversal no Registro Paulista de Cirurgia Cardiovascular II (REPLICCAR II). Os dados perioperatórios de 3122 pacientes foram agrupados pelo número de enxertos arteriais utilizados e seus desfechos foram comparados: reoperação, infecção profunda da ferida torácica (IPFT), acidente vascular cerebral, lesão renal aguda, intubação prolongada (>24 horas), tempo de internação curta (<6 dias), tempo de internação prolongada (>14 dias), morbidade e mortalidade. O Propensity Score Matching (PSM) correspondeu a 1062 pacientes, ajustado para o risco de mortalidade. RESULTADOS: Após PSM, o grupo enxerto arterial único apresentou pacientes com idade avançada, mais ex-fumantes, hipertensos, diabéticos, portadores de angina estável e infarto do miocárdio prévio. Nos enxertos arteriais múltiplos houve predomínio do sexo masculino, pneumonia recente e cirurgias de urgência. Após o procedimento, houve maior incidência de derrame pleural (p=0,042), pneumonia (p=0,01), reintubação (p=0,006), IPFT (p=0,007) e desbridamento esternal (p=0,015) no grupo de enxertos multiarteriais, porém, menor necessidade de hemotransfusão (p=0,005), infecções de extremidades (p=0,002) e menor tempo de internação (p=0,036). O uso bilateral da artéria torácica interna não foi relacionado ao aumento da taxa de IPFT, e sim a hemoglobina glicosilada >6,40% (p=0,048). CONCLUSÃO: Pacientes submetidos a técnica multiarterial apresentaram maior incidência de complicações pulmonares e IPFT, sendo que a hemoglobina glicosilada ≥6,40% teve maior influência no resultado infeccioso do que a escolha dos enxertos.

Activation of the central but not the medial and cortical amygdala during anticipation for daily nursing in the rabbit.

Rabbits have remarkable nursing behavior: after parturition, does visit daily their pups for nursing only once with circadian periodicity. Before the nursing events, they present increased activity and arousal, which shift according to the timing of scheduled nursing, either during the day or night. Brain areas related to maternal behavior and neuroendocrine cells for milk secretion are also entrained. The daily return of the doe for nursing at approximately the same hour suggests a motivational drive with circadian periodicity. Previously, we reported the activation of the mesolimbic system at the time of nursing, but not 12 h before that. Aiming at a better understanding of the mechanism of this anticipatory behavior, we explored the participation of the limbic regions of the amygdala and the bed nucleus of the stria terminalis, as well as the possible activation of the hypothalamic-pituitaryadrenal axis, specifically the corticotropin-releasing factor cells in the hypothalamic paraventricular nucleus of does at different times before and after nursing. The medial and cortical amygdala, the bed nucleus of the stria terminalis, and corticotropin cells showed activation only after nursing. However, the central amygdala was also activated before nursing. We conclude that the medial and the cortical amygdala form part of the afferent olfactory pathway for entrainment, and the central amygdala participates in the anticipatory motivational circuit of the control of periodic nursing. The lack of activation of corticotropin cells before nursing is consistent with the possible harmful effects of the doe's high glucocorticoid levels on the developing pups.

Identification of neural circuits controlling male sexual behavior and sexual motivation by manganese-enhanced magnetic resonance imaging.

Introduction: Different techniques have been used to identify the brain regions that control sexual motivation and sexual behavior. However, the influence of sexual experience on the activation of these brain regions in the same subject is unknown. Using manganese-enhanced magnetic resonance imaging (MEMRI), we analyzed the activation of brain regions in the sexual incentive motivation (SIM) and the partner preference PP (tests) on weeks 1, 5, and 10 in male rats tested for 10 weeks. AIM. In experiment 1, we analyzed the possible toxic effects of 16 mg/kg of MnCl2 on male sexual behavior, running wheel, and motor execution. In experiment 2, subjects were tested for SIM and PP using MEMRI. Methods: In both experiments, a dose of 16 mg/kg (s.c) of chloride manganese (MnCl2) was administered 24 h before subjects were tested and placed immediately thereafter in a 7-Tesla Bruker scanner. Results: In experiment 1, the dose of 16 mg/kg of MnCl2 did not induce behavioral alterations that could interfere with interpreting the imaging data. In experiment 2, we found a clear preference for the female in both the SIM and PP tests. We found a higher signal intensity in the olfactory bulb (OB) in week 1 of the SIM test compared to the control group. We also found increased signal intensity in the socio-sexual behavior and mesolimbic reward circuits in the SIM test in week 1. In the PP test, we found a higher signal intensity in the ventral tegmental area (VTA) in week 10 compared to the control group. In the same test, we found increased signal intensity in the socio-sexual and mesolimbic reward circuits in week 5 compared to the control group. Cohen's d analysis of the whole brain revealed that as the subjects gained sexual experience we observed a higher brain activation in the OB in the SIM group. The PP group showed higher brain activation in the cortex and subcortical structures as they acquired sexual experience. Discussion: As the subjects gain sexual experience, more structures of the reward and socio-sexual circuits are recruited, resulting in different, and large brain activations.

Resultados Imediatos após Múltiplos Enxertos Arteriais em Cirurgia de Revascularização Miocárdica no Estado de São Paulo: Estudo de Coorte / Immediate Results after Multiple Arterial Grafts in Coronary Artery Bypass Graft Surgery in the São Paulo State: Cross Cohort Study

Resumo Fundamento Os resultados a curto prazo após o uso de enxertos arteriais ainda suscitam questionamentos e dúvidas na sociedade médica. Objetivo Comparar os resultados imediatos de pacientes submetidos à cirurgia de revascularização do miocárdio com enxerto arterial único versus enxertos arteriais múltiplos. Métodos Estudo de coorte transversal no Registro Paulista de Cirurgia Cardiovascular II (REPLICCAR II). Os dados perioperatórios de 3122 pacientes foram agrupados pelo número de enxertos arteriais utilizados e seus desfechos foram comparados: reoperação, infecção profunda da ferida torácica (IPFT), acidente vascular cerebral, lesão renal aguda, intubação prolongada (>24 horas), tempo de internação curta (<6 dias), tempo de internação prolongada (>14 dias), morbidade e mortalidade. O Propensity Score Matching (PSM) correspondeu a 1062 pacientes, ajustado para o risco de mortalidade. Resultados Após PSM, o grupo enxerto arterial único apresentou pacientes com idade avançada, mais ex-fumantes, hipertensos, diabéticos, portadores de angina estável e infarto do miocárdio prévio. Nos enxertos arteriais múltiplos houve predomínio do sexo masculino, pneumonia recente e cirurgias de urgência. Após o procedimento, houve maior incidência de derrame pleural (p=0,042), pneumonia (p=0,01), reintubação (p=0,006), IPFT (p=0,007) e desbridamento esternal (p=0,015) no grupo de enxertos multiarteriais, porém, menor necessidade de hemotransfusão (p=0,005), infecções de extremidades (p=0,002) e menor tempo de internação (p=0,036). O uso bilateral da artéria torácica interna não foi relacionado ao aumento da taxa de IPFT, e sim a hemoglobina glicosilada >6,40% (p=0,048). Conclusão Pacientes submetidos a técnica multiarterial apresentaram maior incidência de complicações pulmonares e IPFT, sendo que a hemoglobina glicosilada ≥6,40% teve maior influência no resultado infeccioso do que a escolha dos enxertos.

Abstract Background The short-term results after using arterial grafts still raise questions and doubts for medical society. Objective To compare the immediate outcomes of patients undergoing single arterial graft versus multiple arterial grafts coronary artery bypass grafting surgery. Methods Cross-sectional cohort study in the São Paulo Registry of Cardiovascular Surgery II (REPLICCAR II). Perioperative data from 3122 patients were grouped by the number of arterial grafts used, and their outcomes were compared: reoperation, deep sternal wound infection (DSWI), stroke, acute kidney injury, prolonged intubation (>24 hours), short hospital stay (<6 days), prolonged hospital stay (>14 days), morbidity and mortality. Propensity Score Matching (PSM) matched 1062 patients, adjusted for the mortality risk. Results After PSM, the single arterial graft group showed patients with advanced age, more former smokers, hypertension, diabetes, stable angina, and previous myocardial infarction. In the multiple arterial grafts, there was a predominance of males, recent pneumonia, and urgent surgeries. After the procedure, there was a higher incidence of pleural effusion (p=0.042), pneumonia (p=0.01), reintubation (p=0.006), DSWI (p=0.007), and sternal debridement (p=0.015) in the multiple arterial grafts group, however, less need for blood transfusion (p=0.005), extremity infections (p=0.002) and shorter hospital stays (p=0.036). Bilateral use of the internal thoracic artery was not related to increased DSWI rate, but glycosylated hemoglobin >6.40% (p=0.048). Conclusion Patients undergoing the multiarterial technique had a higher incidence of pulmonary complications, and DSWI, where glycosylated hemoglobin ≥6.40%, had a greater influence on the infectious outcome than the choice of grafts.

Pair-bonding and social experience modulate new neurons survival in adult male and female prairie voles (Microtus ochrogaster).

Prairie voles are a socially monogamous species that, after cohabitation with mating, form enduring pair bonds. The plastic mechanisms involved in this social behavior are not well-understood. Neurogenesis in adult rodents is a plastic neural process induced in specific brain areas like the olfactory bulbs (OB) and dentate gyrus (DG) of the hippocampus. However, it is unknown how cell survival is modulated by social or sexual experience in prairie voles. This study aimed to evaluate if cohabitation with mating and/or social exposure to a vole of the opposite sex increased the survival of the new cells in the main and accessory OB and DG. To identify the new cells and evaluate their survival, voles were injected with the DNA synthesis marker 5-bromo-2'-deoxyuridine (BrdU) and were randomly distributed into one of the following groups: (A) Control (C), voles that did not receive any sexual stimulation and were placed alone during the behavioral test. (B) Social exposure (SE), voles were individually placed in a cage equally divided into two compartments by an acrylic screen with small holes. One male and one female were placed in opposite compartments. (C) Social cohabitation with mating (SCM), animals mated freely. Our findings demonstrated that SCM females had increases in the number of new cells (BrdU-positive cells) in the main olfactory bulb and new mature neurons (BrdU/NeuN-positive cells) in the glomerular layer (GlL). In contrast, these new cells decrease in males in the SE and SCM conditions. In the granular cell layer (GrL), SCM females had more new cells and neurons than the SE group. In the accessory olfactory bulb, in the anterior GlL, SCM decreased the number of new cells and neurons in females. On the other hand, in the DG, SCM and SE increase the number of new cells in the suprapyramidal blade in female voles. Males from SCM express more new cells and neurons in the infrapyramidal blade compared with SE group. Comparison between male and females showed that new cells/neurons survival was sex dependent. These results suggest that social interaction and sexual behavior modulate cell survival and influence the neuronal fate in a sex-dependent manner, in the OB and DG. This study will contribute to understand neural mechanisms of complex social and pair bond behaviors in the prairie voles; supporting adult neurogenesis as a plastic mechanism potentially involved in social monogamous strategy.

Brain circuits activated by female sexual behavior evaluated by manganese enhanced magnetic resonance imaging.

Magnetic resonance imaging (MRI) allows obtaining anatomical and functional information of the brain in the same subject at different times. Manganese-enhanced MRI (MEMRI) uses manganese ions to identify brain activity, although in high doses it might produce neurotoxic effects. Our aims were to identify a manganese dose that does not affect motivated behaviors such as sexual behavior, running wheel and the rotarod test. The second goal was to determine the optimal dose of chloride manganese (MnCl2) that will allow us to evaluate activation of brain regions after females mated controlling (pacing) the sexual interaction. To achieve that, two experiments were performed. In experiment 1 we evaluated the effects of two doses of MnCl2, 8 and 16 mg/kg. Subjects were injected with one of the doses of MnCl2 24 hours before the test on sessions 1, 5 and 10 and immediately thereafter scanned. Female sexual behavior, running wheel and the rotarod were evaluated once a week for 10 weeks. In experiment 2 we followed a similar procedure, but females paced the sexual interaction once a week for 10 weeks and were injected with one of the doses of MnCl2 24 hours before the test and immediately thereafter scanned on sessions 1, 5 and 10. The results of experiment 1 show that neither dose of MnCl2 induces alterations on sexual behavior, running wheel and rotarod. Experiment 2 demonstrated that MEMRI allow us to detect activation of different brain regions after sexual behavior, including the olfactory bulb (OB), the bed nucleus of the stria terminalis (BNST), the amygdala (AMG), the medial preoptic area (MPOA), the ventromedial hypothalamus (VMH), the nucleus accumbens (NAcc), the striatum (STR) and the hippocampus (Hipp) allowing the identification of changes in brain circuits activated by sexual behavior. The socio sexual circuit showed a higher signal intensity on session 5 than the reward circuit and the control groups indicating that even with sexual experience the activation of the reward circuit requires the activation of the socio sexual circuit. Our study demonstrates that MEMRI can be used repeatedly in the same subject to evaluate the activation of brain circuits after motivated behaviors and how can this activation change with experience.

Rabbits can be conditioned in a food-induced place preference paradigm.

The conditioned place preference (CPP) paradigm has been employed in behavioral studies to investigate the responses to an environment where a reinforcing event occurs. It is applied to reveal incentive motivational responses to reward-related stimuli. It is standardized and widely applied in mice and rats, two of the most common species of laboratory animals. However, no studies using the CPP protocol have been performed in rabbits, even though this animal model is commonly used in pharmacological and behavioral research. There are important physiological and behavioral differences between rodents and rabbits. For example, rodents are spontaneous ovulators while rabbits are induced ovulators. In addition, lactation in the rabbit is circadian, which is unique among mammals. The present investigation aims to establish whether rabbits can be conditioned by using a food-induced CPP protocol in subjects with caloric restriction. Adult female rabbits were subjected to a three-compartment CPP protocol. The food produced place preference, demonstrating for the first time that rabbits can be conditioned using the CPP paradigm opening a new field of opportunities for behavioral studies of positive affective states in a species with important behavioral and physiological differences from rodents.

Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α2-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation.

BACKGROUND: Premature ejaculation is the most common sexual dysfunction in young men, and it often leads to reduced relationship satisfaction and quality of life. AIM: To determine the role of central and peripheral α2-adrenoceptors in the control of ejaculation and sexual incentive motivation in rats. METHODS: Sexual incentive motivation was studied in a large arena in which a male subject could choose between approaching and remaining close to a sexually receptive female or another male. Sexual behavior was studied in standard observation cages in which a male was allowed to freely interact with a receptive female for 30 minutes. Two highly selective agonists at the α2-adrenoceptors, tasipimidine and fadolmidine, were administered before the tests. Low peripheral doses of fadolmidine have been reported to have effects mainly outside of the central nervous system, whereas at large doses also the central effects are evident. OUTCOMES: The time spent close to the receptive female in relation to the time spent with the male and measures of ambulatory activity were obtained from the test for sexual incentive motivation, while the habitual parameters of sexual behavior were recorded with the copulation test. RESULTS: Tasipimidine prolonged ejaculation latency and the interintromission interval at the dose of 200 µg/kg when data from fast-ejaculating rats were used. No other sexual parameter was modified. A dose of 100 µg/kg was ineffective. There was no consistent effect on sexual incentive motivation, although modest sedation was observed. Fadolmidine, a drug that does not easily penetrate the blood-brain barrier, had no effect on sexual incentive motivation at any of the doses used (3, 30, and 100 µg/kg). The largest dose had clear sedative effects. The lower doses had no systematic effect on sexual behavior, not even when only fast or very fast ejaculating males were analyzed. CLINICAL TRANSLATION: The findings are relevant to the search for treatments for premature ejaculation that are specific enough to selectively delay ejaculation. STRENGTHS & LIMITATIONS: The procedures used here are standard in the field and yield the most reliable data. Whether the effects observed in male rats are directly transferrable to men can only be determined through clinical studies. CONCLUSION: The observation that drugs acting at central but not peripheral α2-adrenoceptors prolong ejaculation latency without affecting any other parameter of sexual behavior or sexual incentive motivation suggests that this kind of drug may be suitable for treating premature ejaculation. Jyrki L., Elisa V.-A., Xi C., et al. Sexual Incentive Motivation and Copulatory Behavior in Male Rats Treated With the Adrenergic α2-Adrenoceptor Agonists Tasipimidine and Fadolmidine: Implications for Treatment of Premature Ejaculation. J Sex Med 2021;18:1677-1689.

Raised without a father: monoparental care effects over development, sexual behavior, sexual reward, and pair bonding in prairie voles.

Around 5 % of mammals are socially monogamous and both parents provide care to the pups (biparental, BP). Prairie voles are socially monogamous rodents extensively used to understand the neurobiological basis of pair bond formation and the consequences that the absence of one parent has in the offspring. Pair bonding, characterized by selective affiliation with a sexual partner, is facilitated in prairie voles by mating for 6 h or cohabitation without mating for 24 h. It was previously shown that prairie voles raised by their mother alone (monoparental, MP) show delayed pair bond formation upon reaching adulthood. In this study we evaluated the effects of BP and MP care provided on the offspring's development, ability to detect olfactory cues, preference for sexually relevant odors, display of sexual behavior, as well as the rewarding effects of mating. We also measured dopamine and serotonin concentration in the nucleus accumbens (ventral striatum) and dorsal striatum after cohabitation and mating (CM) to determine if differences in these neurotransmitters could underlie the delay in pair bond formation in MP voles. Our data showed that MP voles received less licking/grooming than BP voles, but no developmental differences between groups were found. No differences were found in the detection and discrimination of olfactory cues or preference for sexually relevant odors, as all groups innately preferred opposite sex odors. No differences were found in the display of sexual behavior. However, CM induced reinforcing properties only in BP males, followed by a preference for their sexual partner in BP but not MP males. BP males showed an increase in dopamine turnover (DOPAC/DA and HVA/DA) in the nucleus accumbens in comparison to MP voles. No differences in dopamine, serotonin or their metabolites were found in the dorsal striatum. Our results indicate that MP voles that received less licking behavior exhibit a delay in pair bond formation possibly because the sexual interaction is not rewarding enough.

Brain functional networks associated with social bonding in monogamous voles.

Previous studies have related pair-bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially relevant regions have yet to be described. In this study, we used resting-state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair-bonding. Thirty-two male and female prairie voles were scanned at baseline, 24 hr, and 2 weeks after the onset of cohabitation. By using network-based statistics, we identified that the functional connectivity of a corticostriatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

Differential changes in GAP-43 or synaptophysin during appetitive and aversive taste memory formation.

Association between events in time and space is a major mechanism for all animals, including humans, which allows them to learn about the world and potentially change their behavior in the future to adapt to different environments. Conditioning taste aversion (CTA) is a single-trial learning paradigm where animals are trained to avoid a novel flavor which is associated with malaise. Many variables can be analyzed with this model and the circuits involved are well described. Thus, the amygdala and the gustatory cortex (GC) are some of the most relevant structures involved in CTA. In the present study we focused in plastic changes that occur during appetitive and/or aversive taste memory formation. Previous studies have demonstrated that memory consolidation, in hippocampal dependent paradigms, induces plastic changes like increase in the concentration of proteins considered as markers of neuronal plasticity, such as the growth associated protein 43 (GAP-43) and synaptophysin (SYN). In the present experiment in male rats we evaluated changes in GAP-43 and SYN expression, using immunofluorescence, induce by the formation of aversive and appetitive taste memory. We found that taste aversive memory formation can induce an increase in GAP-43 in the granular layer of the GC. Furthermore, we also found an increase in SYN expression in both layers of the GC, the basolateral amygdala (BLA) and the central amygdala (CeA). These results suggest that aversive memory representation induces a new circuitry (inferred from an increase in GAP 43). On the other hand, an appetitive taste learning increased SYN expression in the GC (both layers), the BLA and the CeA without any changes in GAP 43. Together these results indicate that aversive memory formation induces structural and synaptic changes, while appetitive memory formation induces synaptic changes; suggesting that aversive and appetitive memories require a different set of cortical and amygdala plastic changes.

Culture of Neurospheres Derived from the Neurogenic Niches in Adult Prairie Voles.

Neurospheres are primary cell aggregates that comprise neural stem cells and progenitor cells. These 3D structures are an excellent tool to determine the differentiation and proliferation potential of neural stem cells, as well as to generate cell lines than can be assayed over time. Also, neurospheres can create a niche (in vitro) that allows the modeling of the dynamic changing environment, such as varying growth factors, hormones, neurotransmitters, among others. Microtus ochrogaster (prairie vole) is a unique model for understanding the neurobiological basis of socio-sexual behaviors and social cognition. However, the cellular mechanisms involved in these behaviors are not well known. The protocol aims to obtain neural progenitor cells from the neurogenic niches of the adult prairie vole, which are cultured under non-adherent conditions, to generate neurospheres. The size and number of neurospheres depend on the region (subventricular zone or dentate gyrus) and sex of the prairie vole. This method is a remarkable tool to study sex-dependent differences in neurogenic niches in vitro and the neuroplasticity changes associated with social behaviors such as pair bonding and biparental care. Also, cognitive conditions that entail deficits in social interactions (autism spectrum disorders and schizophrenia) could be examined.

Repeated Paced Mating Increases the Survival of New Neurons in the Accessory Olfactory Bulb.

In female rats, the first sexual experience under paced mating conditions increases the number of newborn cells that migrate into the granular layer of the accessory olfactory bulb (AOB). Repeated paced mating has a potentiating effect on the number of new neurons that migrate to the AOB compared with a single session 15 days after paced mating. On the other hand, one paced mating session does no increases the survival of new cells 45 days after mating. In the present study, we evaluated if four paced mating sessions could increase the survival of new neurons in the AOB and main olfactory bulb (MOB) 45 days after females mated. Sexually naive female rats were ovariectomized, hormonally supplemented and randomly assigned to one of five groups: (1) Control, no sexual contact (C); (2) Four sessions in which females were exposed, without mating, to a sexually experience male rat (SE); (3) One session of paced mating (PM1); (4) Four sessions of paced mating (PM4); and (5) Four sessions of non-paced mating (NPM4). In the first behavioral test, females received the DNA synthesis marker 5-bromo-2'deoxyuridine and were euthanized 45 days later. Our data showed that the number of new cells that survived in the mitral cell layer of the AOB decreased when females were exposed to a sexually active male, in comparison to females that mated once pacing the sexual interaction. Repeated sexual behavior in pacing conditions did not increase the survival of new cells in other layers of the MOB and AOB. However, a significant increase in the percentage of new neurons in the granular and glomerular layers of the AOB and granular layer of the MOB was observed in females that mated in four sessions pacing the sexual interaction. In the group that paced the sexual interaction for one session, a significant increase in the percentage of neurons was observed in the glomerular layer of the AOB. Our data suggest that repeated paced mating increases the percentage of new neurons that survive in the olfactory bulb of female rats.

Sexual behavior in rodents: Where do we go from here?

Hormones and Behavior was first published 50 years ago including some articles related to the hormonal regulation of sexual behavior in different species. Since then, this research field has produced outstanding discoveries that have contributed to our understanding of the control of sexual behavior. The refinement of classical techniques and the development of new experimental tools has opened the door to a new era of research that will allow us to understand different aspects of sexual behavior. It would also expand the possible extrapolation from animal models to understand human sexuality and its dysfunctions. In this review, we summarize some of the most recent findings about sexual behavior in both sexes including the refinement of classical methods of study with new approaches and questions as well as the development of new methods trying to explain mechanisms of action on motivational and consummatory elements of mating behavior. We also reviewed other aspects that modulate sexual behavior such as attractivity, olfactory signals and learning which model mate selection. Additionally, we described studies demonstrating that sexual behavior induces permanent brain modifications in neuronal circuits. Finally, we briefly describe recent contributions on animal models of human sexuality dysfunctions which, although with their own limitations, are under continuous refining.

Preterm newborns undergoing selective correction surgery of the patent ductus arteriosus: is there still space for these procedures? / Recém-nascidos pré-termos submetidos à cirurgia seletiva da persistência do canal arterial: ainda há espaço para esses procedimentos?

INTRODUCTION: The ductus arteriosus is a small fetal structure that connects two large arteries (aorta and pulmonary) but becomes pathological when it is maintained after birth. Morbidities associated with persistent patent ductus arteriosus (PDA) may lead to the conclusion that the best approach is early surgical treatment. However, there is evidence that expectant (more selective) surgical management may reduce the chances of unnecessary surgeries and their risks. OBJECTIVE: To analyze the clinical and surgical profile of preterm newborns submitted to selective correction surgery of the patent ductus arteriosus. METHODS: This paper contemplates a series of cases, in which all patients submitted to the surgical treatment of PDA in preterm infants were described retrospectively (2009-2016), through the analysis of medical records of the Santa Marcelina Hospital, SP-Brazil. RESULTS: During this period, there were 13 cases of premature infants who underwent selective surgical correction of PDA. Gestational age was 26.92 weeks, maternal age ranged from 15 to 44, birth weight varied between 650 and 1500g, mostly women (61.54%). The diameter of the ductus arteriosus ranged from 1.7 to 4.1 mm, four patients had complex congenital heart disease (30.77%). The median courses of indomethacin were 1.77, congestive heart failure was shown in 11 patients (84.62%), the median age at surgery was 27.69 days and the median duration of orotracheal intubation was 22.62 days. The weight of the newborns at the time of the surgical act varied between 900 and 1820g. The postoperative complications were mostly infectious, with nine patients with bronchopneumonia (69.23%), one patient had pneumothorax. Sepsis occurred in two cases (15.35%) that died due to the same complication (15.35%). CONCLUSION: All preterm newborns who underwent surgery had birth weight less than 1500g. The median arterial canal was 3.05 mm in diameter. The median gestational age was 26.92 weeks and 62% of the cases were female. The most frequent surgical technique was the triple clipping, there was no bleeding or reoperation in this series of cases.

INTRODUÇÃO: O canal arterial é uma pequena estrutura fetal que comunica duas grandes artérias (aorta e pulmonar), mas que se torna patológica quando se mantem após o nascimento. As morbidades associadas à persistência do canal arterial (PCA) podem levar à conclusão de que a melhor conduta seja o tratamento cirúrgico precoce. No entanto, há evidências de que a conduta cirúrgica expectante (seletiva), poderia diminuir os riscos de cirurgias desnecessárias e suas complicações OBJETIVO: Analisar o perfil clínico-cirúrgico dos recém-nascidos pré-termos (RNPT) submetidos à cirurgia seletiva de correção da Persistência do Canal Arterial MÉTODO: Este trabalho contempla uma série de casos, onde foram descritos retrospectivamente (2009-2016) todos os recém-nascidos submetidos ao tratamento cirúrgico de PCA em RNPT através da análise de prontuários do Hospital Santa Marcelina, SP-Brasil RESULTADOS: Neste período, observou-se 13 casos de prematuros que foram submetidos à correção cirúrgica seletiva da PCA. A idade gestacional média foi de 26,92 semanas, a idade materna variou entre 15 e 44 anos. O peso ao nascimento variou entre 650 e 1500g e houve prevalência do sexo feminino (61,54%). O diâmetro do canal arterial variou entre 1,7 e 5 mm, quatro recém-nascidos apresentaram cardiopatia congênita complexa (30,77%). A média de ciclos de indometacina foi de 1,77. A insuficiência cardíaca congestiva se evidenciou em 11 recém-nascidos (84,62%); a idade média no ato cirúrgico foi de 27,69 dias e a média do tempo de intubação orotraqueal foi de 22,62 dias. O peso no momento do ato cirúrgico variou entre 900 e 1820g. As complicações pós-operatórias foram em sua maioria infecciosas, observando-se nove recém-nascidos com broncopneumonia (69,23%); um paciente apresentou pneumotórax. Ocorreram sepse em dois casos (15,35%) que evoluíram para óbito por esta mesma complicação (15,35% CONCLUSÃO: Todos os RNPT que foram submetidos a cirurgia tiveram peso ao nascimento menor de 1500g. A média de canal arterial foi de 3,05 mm de diâmetro. A idade gestacional média foi de 26,92 semanas e 62% dos casos eram do sexo feminino. A técnica cirúrgica mais frequente foi a da tripla clipagem, não houve sangramento ou reoperação nesta série de casos. A cirurgia seletiva de PCA ainda se faz necessária nos dias atuais

Motivational Drive in Non-copulating and Socially Monogamous Mammals.

Motivational drives guide behaviors in animals of different species, including humans. Some of these motivations, like looking for food and water, are crucial for the survival of the individual and hence for the preservation of the species. But there is at least another motivation that is also important for the survival of the species but not for the survival of the individual. Undoubtedly, sexual motivation is important for individuals to find a mate and reproduce, thus ensuring the survival of the species. In species with sexual reproduction, when males find a female in the appropriate hormonal conditions, they will display sexual behavior. However, some healthy males do not mate when they have access to a sexually receptive female, even though they are repeatedly tested. These non-copulating (NC) individuals have been reported in murine, cricetid and ungulates. In humans this sexual orientation is denominated asexuality. Asexual individuals are physically and emotionally healthy men and women without desire for sexual intercourse. Different species have developed a variety of strategies to find a mate and reproduce. Most species of mammals are polygamous; they mate with one or several partners at the same time, as occur in rats, or they can reproduce with different conspecifics throughout their life span. There are also monogamous species that only mate with one partner. One of the most studied socially monogamous species is the Prairie vole. In this species mating or cohabitation for long periods induces the formation of a long-lasting pair bond. Both males and females share the nest, show a preference for their sexual partner, display aggression to other males and females and display parental behavior towards their pups. This broad spectrum of reproductive strategies demonstrates the biological variability of sexual motivation and points out the importance of understanding the neurobiological basis of sexual motivational drives in different species.