RESUMO
The mesocorticolimbic system coordinates executive functions, such as working memory and behavioral flexibility. This circuit includes dopaminergic projections from the ventral tegmental area to the nucleus accumbens and medial prefrontal cortex. In this review, we summarize evidence that cells in multiple nodes of the mesocorticolimbic system produce neurosteroids (steroids synthesized in the nervous system) and express steroid receptors. Here, we focus on neuroandrogens (androgens synthesized in the nervous system), neuroestrogens (estrogens synthesized in the nervous system), and androgen and estrogen receptors. We also summarize how (neuro)androgens and (neuro)estrogens affect dopamine signaling in the mesocorticolimbic system and regulate executive functions. Taken together, the data suggest that steroids produced in the gonads and locally in the brain modulate higher-order cognition and executive functions.
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Behavioural flexibility is essential to adapt to a changing environment and depends on the medial prefrontal cortex (mPFC). Testosterone administration decreases behavioural flexibility. It is well known that testosterone is produced in the gonads, but testosterone is also produced in the brain, including the mPFC and other nodes of the mesocorticolimbic system. It is unclear how testosterone produced in the brain versus the gonads influences behavioural flexibility. Here, in adult male rats, we assessed the effects of the androgen synthesis inhibitor abiraterone acetate (ABI) and long-term gonadectomy (GDX) on behavioural flexibility in two paradigms. In Experiment 1, ABI but not GDX reduced the number of errors to criterion and perseverative errors in a strategy set-shifting task. In Experiment 2, with a separate cohort of rats, ABI but not GDX reduced perseverative errors in a reversal learning task. In Experiment 1, we also examined tyrosine hydroxylase immunoreactivity (TH-ir), and ABI but not GDX increased TH-ir in the mPFC. Our findings suggest that neurally-produced androgens modulate behavioural flexibility via modification of dopamine signalling in the mesocorticolimbic system. These results indicate that neurosteroids regulate executive functions and that ABI treatment for prostate cancer might affect cognition.
Assuntos
Androgênios , Tirosina 3-Mono-Oxigenase , Androgênios/farmacologia , Animais , Masculino , Córtex Pré-Frontal/fisiologia , Ratos , Reversão de Aprendizagem , Testosterona/fisiologiaRESUMO
Maternal diets can have dramatic effects on the physiology, metabolism, and behaviour of offspring that persist into adulthood. However, the effects of maternal sucrose consumption on offspring remain unclear. Here, female rats were fed either a sucrose diet with a human-relevant level of sucrose (25% of kcal) or a macronutrient-matched, isocaloric control diet before, during, and after pregnancy. After weaning, all offspring were fed a standard low-sucrose rodent chow. We measured indicators of metabolism (weight, adipose, glucose tolerance, and liver lipids) during development and adulthood (16-24 weeks). We also measured food preference and motivation for sugar rewards in adulthood. Finally, in brain regions regulating these behaviours, we measured steroids and transcripts for steroidogenic enzymes, steroid receptors, and dopamine receptors. In male offspring, maternal sucrose intake decreased body mass and visceral adipose tissue, increased preference for high-sucrose and high-fat diets, increased motivation for sugar rewards, and decreased mRNA levels of Cyp17a1 (an androgenic enzyme) in the nucleus accumbens. In female offspring, maternal sucrose intake increased basal corticosterone levels. These data demonstrate the enduring, diverse, and sex-specific effects of maternal sucrose consumption on offspring phenotype.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Fenômenos Fisiológicos da Nutrição Pré-Natal , Esteroides/metabolismo , Sacarose/administração & dosagem , Ração Animal , Animais , Biomarcadores , Comportamento de Escolha/efeitos dos fármacos , Dieta , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismoRESUMO
Many animal species have evolved extreme behaviors requiring them to engage in repeated high-impact collisions. These behaviors include mating displays like headbutting in sheep and drumming in woodpeckers. To our knowledge, these taxa do not experience any notable acute head trauma, even though the deceleration forces would cause traumatic brain injury in most animals. Previous research has focused on skeletomuscular morphology, biomechanics, and material properties in an attempt to explain how animals moderate these high-impact forces. However, many of these behaviors are understudied, and most morphological or computational studies make assumptions about the behavior without accounting for the physiology of an organism. Studying neurophysiological and immune adaptations that covary with these behaviors can highlight unique or synergistic solutions to seemingly deleterious behavioral displays. Here, we argue that selection for repeated, high-impact head collisions may rely on a suite of coadaptations in intracranial physiology as a cost-reducing mechanism. We propose that there are three physiological systems that could mitigate the effects of repeated head trauma: (1) the innate neuroimmune response; (2) the glymphatic system, and (3) the choroid plexus. These systems are interconnected yet can evolve in an independent manner. We then briefly describe the function of these systems, their role in head trauma, and research that has examined how these systems may evolve to help reduce the cost of repeated, forceful head impacts. Ultimately, we note that little is known about cost-reducing intracranial mechanisms making it a novel field of comparative study that is ripe for exploration.
Assuntos
Lesões Encefálicas Traumáticas , Traumatismos Craniocerebrais , Doenças dos Ovinos , Animais , Fenômenos Biomecânicos , Neurofisiologia , Fenótipo , OvinosRESUMO
Gestural communication is ubiquitous throughout the animal kingdom, occurring in species that range from humans to arthropods. Individuals produce gestural signals when their nervous system triggers the production of limb and body movement, which in turn functions to help mediate communication between or among individuals. Like many stereotyped motor patterns, the probability of a gestural display in a given social context can be modulated by sex steroid hormones. Here, we review how steroid hormones mediate the neural mechanisms that underly gestural communication in humans and nonhumans alike. This is a growing area of research, and thus we explore how sex steroids mediate brain areas involved in language production, social behavior, and motor performance. We also examine the way that sex steroids can regulate behavioral output by acting in the periphery via skeletal muscle. Altogether, we outline a new avenue of behavioral endocrinology research that aims to uncover the hormonal basis for one of the most common modes of communication among animals on Earth.
Assuntos
Comunicação Animal , Gestos , Hormônios Esteroides Gonadais/fisiologia , Animais , Evolução Biológica , Sistema Nervoso Central/fisiologia , HumanosRESUMO
Performance trade-offs can dramatically alter an organism's evolutionary trajectory by making certain phenotypic outcomes unattainable. Understanding how these trade-offs arise from an animal's design is therefore an important goal of biology. To explore this topic, we studied how androgenic hormones, which regulate skeletal muscle function, influence performance trade-offs relevant to different components of complex reproductive behaviour. We conducted this work in golden-collared manakins (Manacus vitellinus), a neotropical bird in which males court females by rapidly snapping their wings together above their back. Androgens help mediate this behavior by radically increasing the twitch speed of a dorsal wing muscle (scapulohumeralis caudalis, SH), which actuates the bird's wing-snap. Through hormone manipulations and in situ muscle recordings, we tested how these positive effects on SH speed influence trade-offs with endurance. Indeed, this latter trait impacts the display by shaping signal length. We found that androgen-dependent increases in SH speed incur a cost to endurance, particularly when this muscle performs at its functional limits. Moreover, when behavioural data were overlaid on our muscle recordings, displaying animals appeared to balance display speed with fatigue-induced muscle fusion (physiological tetanus) to generate the fastest possible signal while maintaining an appropriate signal duration. Our results point to androgen action as a functional trigger of trade-offs in sexual performance - these hormones enhance one element of a courtship display, but in doing so, impede another.
Assuntos
Androgênios , Passeriformes , Animais , Corte , Feminino , Masculino , Músculo Esquelético , Comportamento Sexual AnimalRESUMO
Sucrose consumption is associated with type 2 diabetes, cardiovascular disease, and cognitive deficits. Sucrose intake during pregnancy might have particularly prominent effects on metabolic, endocrine, and neural physiology. It remains unclear how consumption of sucrose affects parous females, especially in brain circuits that mediate food consumption and reward processing. Here, we examine whether a human-relevant level of sucrose before, during, and after pregnancy (17-18 weeks total) influences metabolic and neuroendocrine physiology in female rats. Females were fed either a control diet or a macronutrient-matched, isocaloric sucrose diet (25% of kcal from sucrose). Metabolically, sucrose impairs glucose tolerance, increases liver lipids, and increases a marker of adipose inflammation, but has no effect on body weight or overall visceral adiposity. Sucrose also decreases corticosterone levels in serum but not in the brain. Sucrose increases progesterone levels in serum and in the brain and increases the brain:serum ratio of progesterone in the mesocorticolimbic system and hypothalamus. These data suggest a dysregulation of systemic and local steroid signalling. Moreover, sucrose decreases tyrosine hydroxylase (TH), a catecholamine-synthetic enzyme, in the medial prefrontal cortex. Finally, sucrose consumption alters the expression pattern of FOSB, a marker of phasic dopamine signalling, in the nucleus accumbens. Overall, chronic consumption of sucrose at a human-relevant level alters metabolism, steroid levels, and brain dopamine signalling in a female rat model.
Assuntos
Encéfalo/metabolismo , Corticosterona/metabolismo , Sacarose Alimentar/farmacologia , Dopamina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Ingestão de Alimentos/fisiologia , Feminino , Modelos Animais , Gravidez , RatosRESUMO
As males age, systemic testosterone (T) levels decline. T regulates executive function, a collection of cognitive processes that are mediated by the mesocorticolimbic system. Here, we examined young adult (5 months) and aged (22 months) male Fischer 344 × Brown Norway rats, and measured systemic T levels in serum and local T levels in microdissected nodes of the mesocorticolimbic system (ventral tegmental area (VTA), nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC)). We also measured androgen receptor (AR) immunoreactivity (-ir) in the mesocorticolimbic system. As expected, systemic T levels decreased with age. Local T levels in mesocorticolimbic regions - except the VTA - also decreased with age. Mesocorticolimbic T levels were higher than serum T levels at both ages. AR-ir was present in the VTA, NAc, mPFC, and OFC and decreased with age in the mPFC. Taken together with previous results, the data suggest that changes in androgen signaling may contribute to changes in executive function during aging.
Assuntos
Envelhecimento/metabolismo , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores Androgênicos/metabolismo , Testosterona/sangue , Área Tegmentar Ventral/metabolismo , Envelhecimento/sangue , Animais , Comportamento Animal/fisiologia , Função Executiva/fisiologia , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344RESUMO
The medial amygdala (MeA), bed nucleus of the stria terminalis (BNST), and medial preoptic area (mPOA) are important for the regulation of male sexual behavior. Sexual experience facilitates sexual behaviors and influences activity in these regions. The goal of this study was to determine whether sexual experience or copulation induces plasticity in the MeA, BNST, or mPOA of male rats, as indicated by changes in levels of Arc, which is indicative of activity-dependent synaptic plasticity in the brain. To this end, sexually naïve or experienced males were placed in mating arenas either alone, with an inaccessible estrus female, or with an accessible estrus female. Arc protein levels were then quantified in these three regions using immunohistochemistry. As expected, sexual experience facilitated copulation, as evidenced by a reduction in latencies to mount, intromit, and ejaculate. Copulation also increased the number of Arc-positive cells in the MeA, anterior BNST, posterior BNST, and the posterior mPOA, but not in the central-rostral region of the mPOA. Surprisingly, prior sexual experience did not impact levels of Arc, suggesting that copulation-induced Arc occurs in both sexually naïve and experienced males.
Assuntos
Copulação/fisiologia , Proteínas do Citoesqueleto/genética , Regulação da Expressão Gênica/genética , Proteínas do Tecido Nervoso/genética , Tonsila do Cerebelo/metabolismo , Animais , Encéfalo/metabolismo , Proteínas do Citoesqueleto/metabolismo , Expressão Gênica/genética , Genes Precoces/genética , Masculino , Proteínas do Tecido Nervoso/metabolismo , Vias Neurais/metabolismo , Área Pré-Óptica/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Long-Evans , Reprodução/genética , Reprodução/fisiologia , Núcleos Septais/metabolismo , Comportamento Sexual Animal/fisiologiaRESUMO
Aging is associated with changes in executive functioning and the mesocorticolimbic dopamine system. However, the effects of aging on different forms of behavioral flexibility are not fully characterized. In young (â¼5 months) and aged (â¼22 months) male Fischer 344 × brown Norway rats, we assessed spatial working memory and different forms of behavioral flexibility using operant tasks: strategy set-shifting (study 1) or probabilistic reversal learning (study 2). We also assessed dopaminergic markers using immunohistochemistry. Compared with young rats, aged rats displayed impairments in working memory. Aged rats also showed nonperseverative impairments in set-shifting, with a subset also showing impairments in initial discrimination learning. In probabilistic reversal learning, aged rats completed more reversals, driven by an increased sensitivity to recent reward and negative feedback. Tyrosine hydroxylase (TH) showed region-specific changes with aging and was correlated with several measures of behavioral flexibility. These data suggest that age-related changes prefrontal cortical function and dopamine synthesis contribute to changes in executive functioning during aging.
Assuntos
Envelhecimento/fisiologia , Dopamina/metabolismo , Função Executiva/fisiologia , Aprendizagem/fisiologia , Memória de Curto Prazo/fisiologia , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Área Tegmentar Ventral/metabolismo , Animais , Comportamento Animal/fisiologia , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344 , Memória Espacial/fisiologiaRESUMO
Multiple lines of evidence indicate that androgens, such as testosterone, modulate the mesocorticolimbic system and executive function. This review integrates neuroanatomical, molecular biological, neurochemical, and behavioral studies to highlight how endogenous and exogenous androgens alter behaviors, such as behavioral flexibility, decision making, and risk taking. First, we briefly review the neuroanatomy of the mesocorticolimbic system, which mediates executive function, with a focus on the ventral tegmental area (VTA), nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Second, we present evidence that androgen receptors (AR) and other steroid receptors are expressed in the mesocorticolimbic system. Using sensitive immunohistochemistry and quantitative polymerase chain reaction (qPCR) techniques, ARs are detected in the VTA, NAc, mPFC, and OFC. Third, we describe recent evidence for local androgens ("neuroandrogens") in the mesocorticolimbic system. Steroidogenic enzymes are expressed in mesocorticolimbic regions. Furthermore, following long-term gonadectomy, testosterone is nondetectable in the blood but detectable in the mesocorticolimbic system, using liquid chromatography tandem mass spectrometry. However, the physiological relevance of neuroandrogens remains unknown. Fourth, we review how anabolic-androgenic steroids (AAS) influence the mesocorticolimbic system. Fifth, we describe how androgens modulate the neurochemistry and structure of the mesocorticolimbic system, particularly with regard to dopaminergic signaling. Finally, we discuss evidence that androgens influence executive functions, including the effects of androgen deprivation therapy and AAS. Taken together, the evidence indicates that androgens are critical modulators of executive function. Similar to dopamine signaling, there might be optimal levels of androgen signaling within the mesocorticolimbic system for executive functioning. Future studies should examine the regulation and functions of neurosteroids in the mesocorticolimbic system, as well as the potential deleterious and enduring effects of AAS use.
RESUMO
Steroid hormones can modulate motivated behaviors through the mesocorticolimbic system. Gonadectomy (GDX) is a common method to determine how steroids influence the mesocorticolimbic system, and caloric restriction (CR) is often used to invigorate motivated behaviors. A common assumption is that the effects of these manipulations on brain steroid levels reflects circulating steroid levels. We now know that the brain regulates local steroid levels in a region-specific manner; however, previous studies have low spatial resolution. Using ultrasensitive liquid chromatography tandem mass spectrometry, we examined steroids in microdissected regions of the mesocorticolimbic system (ventral tegmental area, nucleus accumbens, medial prefrontal cortex). We examined whether GDX or CR influences systemic and local steroids, particularly testosterone (T) and steroidogenic enzyme transcripts. Adult male rats underwent a GDX surgery and/or CR for either 2 or 6 weeks. Levels of T, the primary steroid of interest, were higher in all brain regions than in the blood, whereas corticosterone (CORT) was lower in the brain than in the blood. Importantly, GDX completely eliminated T in the blood and lowered T in the brain. Yet, T remained present in the brain, even 6 weeks after GDX. CR decreased both T and CORT in the blood and brain. Steroidogenic enzyme (Cyp17a1, 3ß-hydroxysteroid dehydrogenase, aromatase) transcripts and androgen receptor transcripts were expressed in the mesocorticolimbic system and differentially affected by GDX and CR. Together, these results suggest that T is synthesized within the mesocorticolimbic system. These results provide a foundation for future studies examining how neurosteroids influence behaviors mediated by the mesocorticolimbic system.
Assuntos
Corticosterona/metabolismo , Neurônios Dopaminérgicos/metabolismo , Sistema Límbico/metabolismo , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Testosterona/metabolismo , Área Tegmentar Ventral/metabolismo , 3-Hidroxiesteroide Desidrogenases/genética , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Aromatase/genética , Aromatase/metabolismo , Restrição Calórica/efeitos adversos , Corticosterona/sangue , Neurônios Dopaminérgicos/enzimologia , Regulação Enzimológica da Expressão Gênica , Sistema Límbico/enzimologia , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Núcleo Accumbens/enzimologia , Orquiectomia/efeitos adversos , Córtex Pré-Frontal/enzimologia , Distribuição Aleatória , Ratos Long-Evans , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/sangue , Área Tegmentar Ventral/enzimologia , Aumento de PesoRESUMO
Testosterone is the main circulating steroid hormone in males, and acts to facilitate sexual behavior via both reduction to dihydrotestosterone (DHT) and aromatization to estradiol. The mPOA is a key site involved in mediating actions of androgens and estrogens in the control of masculine sexual behavior, but the respective roles of these hormones is not fully understood. As males age they show impairments in sexual function, and a decreased facilitation of behavior by steroid hormones compared to younger animals. We hypothesized that an anatomical substrate for these behavioral changes is a decline in expression and/or activation of hormone receptor-sensitive cells in the mPOA. We tested this by quantifying and comparing numbers of AR- and ERα-containing cells, and Fos as a marker of activated neurons, in the mPOA of mature (4-5months) and aged (12-13months) male rats, assessed one hour after copulation to one ejaculation. Numbers of AR- and ERα cells did not change with age or after sex, but the percentage of AR- and ERα-cells that co-expressed Fos were significantly up-regulated by sex, independent of age. Age effects were found for the percentage of Fos cells that co-expressed ERα (up-regulated in the central mPOA) and the percentage of Fos cells co-expressing AR in the posterior mPOA. Interestingly, serum estradiol concentrations positively correlated with intromission latency in aged but not mature animals. These data show that the aging male brain continues to have high expression and activation of both AR and ERα in the mPOA with copulation, raising the possibility that differences in relationships between hormones, behavior, and neural activation may underlie some age-related impairments.
Assuntos
Envelhecimento/fisiologia , Área Pré-Óptica/metabolismo , Receptores Androgênicos/metabolismo , Receptores de Estrogênio/metabolismo , Comportamento Sexual Animal/fisiologia , Animais , Di-Hidrotestosterona/sangue , Estradiol/sangue , Masculino , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Testosterona/sangueRESUMO
Dopamine in the medial preoptic area (mPOA) stimulates sexual activity in males. This is evidenced by microdialysis and microinjection experiments revealing that dopamine receptor antagonists in the mPOA inhibit sexual activity, whereas agonists facilitate behavior. Microdialysis experiments similarly show a facilitative role for dopamine, as levels of dopamine in the mPOA increase with mating. While the majority of evidence suggests an important role for dopamine receptors in the mPOA in the regulation of male sexual behaviors, whether sexual activity or sexual experience influence dopamine receptor function in the mPOA has not been previously shown. Here we used immunohistochemical assays to determine whether varying levels of sexual activity or experience influence the number of cells containing Fos or D2 receptor immunoreactivity. Results show that sexual experience facilitated subsequent behavior, namely experience decreased latencies. Moreover, the number of cells with immunoreactivity for Fos or D2 correlated with levels of sexual experience and sexual activity. Sexual activity increased Fos immunoreactivity. Sexually experienced animals also had significantly more D2-positive cells. Sexually inexperienced animals copulating for the first time had a larger percentage of D2-positive cells containing Fos, when compared to sexually experienced animals. Finally, regardless of experience, animals that had sex prior to sacrifice had significantly more D2-positive cells that contained Fos, vs. animals that did not copulate. These findings are noteworthy because sexually experienced animals display increased sexual efficiency. The differences in activation of D2 and changes in receptor density may play a role in this efficiency and other behavioral changes across sexual experience.
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The sex-steroid hormone estradiol (E2) enhances the psychoactive effects of cocaine, as evidenced by clinical and preclinical studies. The medial preoptic area (mPOA), a region in the hypothalamus, is a primary neural locus for neuroendocrine integration, containing one of the richest concentrations of estrogen receptors in the CNS and also has a key role in the regulation of naturally rewarding behaviors. However, whether estradiol enhances the neurochemical response to cocaine by acting in the mPOA is still unclear. Using neurotoxic lesions and microdialysis, we examined whether the mPOA modulates cocaine-induced neurochemical activity in the nucleus accumbens. Tract tracing and immunohistochemical staining were used to determine whether projections from the mPOA to the ventral tegmental area (VTA) are sensitive to estrogen signaling. Finally, estradiol microinjections followed by microdialysis were used to determine whether estrogenic signaling in the mPOA modulates cocaine-induced changes of dopamine in the nucleus accumbens. Results showed that lesions of the mPOA or microinjections of estradiol directly into the mPOA increased cocaine-induced release of dopamine in the nucleus accumbens. Immunohistochemical analyses revealed that the mPOA modulates cocaine responsiveness via projections to both dopaminergic and GABAergic neurons in the VTA, and that these projections are sensitive to estrogenic stimulation. Taken together, these findings point to a novel estradiol-dependent pathway that modulates cocaine-induced neurochemical activity in the mesolimbic system.
Assuntos
Anestésicos Locais/farmacologia , Cocaína/farmacologia , Dopamina/metabolismo , Estradiol/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Análise de Variância , Animais , Agonistas de Aminoácidos Excitatórios/toxicidade , Feminino , Microdiálise , N-Metilaspartato/toxicidade , Núcleo Accumbens/fisiologia , Ovariectomia , Fosfopiruvato Hidratase/metabolismo , Área Pré-Óptica/lesões , Área Pré-Óptica/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Estilbamidinas/farmacocinética , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
While sexually experienced males copulate at a higher frequency than sexually inexperienced males, there is still a great deal of variability in their behavior. Within the medial preoptic area (mPOA) of the hypothalamus, glutamate modulates some of this variability. Glutamate levels, for example, increase during sexual activity, peaking with ejaculation and falling precipitously during the post-ejaculation interval. Whereas lower glutamate levels after ejaculation translates to longer post-ejaculatory intervals, administration of glutamate uptake inhibitors into the mPOA increases the number of ejaculations a male rat achieves over a mating bout, and reduces the latency to ejaculate once mating begins. Because astrocytes modulate the availability of neuronal glutamate, we hypothesized that differences in the number of GFAP-positive astrocytes in the mPOA may account for variability in sexual behavior. To this end, we examined whether the number of astrocytes in the mPOA related to ejaculation latency as well as to the duration of the post-ejaculatory interval (PEI) in sexually experienced and sexually inexperienced males. Results indicate that the number of astrocytes negatively correlated with latency to reach ejaculations in sexually inexperienced but not sexually experienced rats while the number of astrocytes and PEI were not related. Astrocyte numbers did not vary between inexperienced and experienced subjects indicating that astrocyte processes may differentially project to sex-relevant glutamatergic synapses or that glutamatergic innervation of the mPOA changes as a function of sexual experience.
Assuntos
Astrócitos/citologia , Copulação/fisiologia , Ejaculação , Área Pré-Óptica/citologia , Animais , Astrócitos/metabolismo , Contagem de Células , Proteína Glial Fibrilar Ácida/metabolismo , Masculino , Área Pré-Óptica/metabolismo , Ratos , Ratos Long-EvansRESUMO
Nitric oxide (NO) acts in the medial preoptic area (mPOA) of the hypothalamus to facilitate the expression of male sexual behavior and has also been widely implicated in mechanisms of experience, learning, and memory. Using immunohistochemistry for Fos, as a marker for neural activity, and nitric oxide synthase (NOS), the enzyme that catalyzes the production of nitric oxide (NO), we examined whether sexual activity and sexual experience influence Fos co-expression in NOS-containing neurons in the mPOA of male rats. Consistent with previous findings, results indicate that mating increased activity in the mPOA, and that sexual experience facilitated the expression of sexual behaviors, together with increased mating-induced Fos and NOS in the mPOA. Results also indicate that mating increased co-expression of Fos in NOS-containing neurons, and that this increase was highest in animals undergoing their first sexual encounter, indicating that initial sexual experience increases NO production in the mPOA of male rats.
Assuntos
Neurônios/enzimologia , Óxido Nítrico Sintase/metabolismo , Área Pré-Óptica/enzimologia , Comportamento Sexual Animal/fisiologia , Animais , Contagem de Células , Ejaculação/fisiologia , Ácido Glutâmico/metabolismo , Masculino , Área Pré-Óptica/química , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Long-EvansRESUMO
Drugs of abuse exert their effects by exploiting natural neurobiological reward mechanisms, especially the mesolimbic dopamine (DA) system. However, the mesolimbic system does not operate in isolation, and input from other reward-relevant structures may play a role in cocaine's rewarding effects. The medial preoptic area (mPOA) of the hypothalamus is involved in the regulation of two essential and naturally rewarding behaviors: sexual and maternal behaviors. It also makes strong neuroanatomical connections with areas of the mesolimbic system, particularly the ventral tegmental area (VTA). As such, the mPOA is a logical candidate for a neuroanatomical locus modulating activity in the mesolimbic system and emergent behavioral expressions of drug reward, yet the role of this structure is largely unexplored. Here, using a female rat model, we show that the mPOA innervates the VTA in a region-specific manner, that lesions of the mPOA augment cocaine-induced Fos expression in the nucleus accumbens (NAc) and cocaine-induced conditioned place preference. We also show that approximately 68% of mPOA-VTA efferents release γ-aminobutyric acid (GABA), over 75% are sensitive to DA as evidenced by colocalization with DA receptors, and nearly 60% of these contain both DA receptors and GABA, which suggests a novel key role for the mPOA in the inhibition of the mesolimbic DA circuit. Combined, these results reveal the mPOA as a critical modulating structure in cocaine-induced mesolimbic activity and behavioral manifestation of reward, at least in part, via GABAergic output that is sensitive to DA input.
Assuntos
Cocaína/farmacologia , Condicionamento Operante/efeitos dos fármacos , Inibidores da Captação de Dopamina/farmacologia , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Área Pré-Óptica/efeitos dos fármacos , Animais , Condicionamento Operante/fisiologia , Dopamina/metabolismo , Feminino , Atividade Motora/fisiologia , Neurônios/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Área Pré-Óptica/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Dopaminérgicos/metabolismo , Recompensa , Ácido gama-Aminobutírico/metabolismoRESUMO
Chemosensory stimulation is vital for the expression of rodent sexual behavior. As sexual activity decreases with aging, this study investigated whether aging also impacts the integration of sex-relevant chemosensory cues. To this end, several measures were obtained from adult (10-12 months) and aged (30-36 months) male rats after exposure to a conspecific estrous female. These included rates of investigatory behaviors, levels of stimulus-induced Fos immunoreactivity, activation of gonadotropin-releasing hormone-containing cells, and levels of circulating testosterone and corticosterone. The results indicated no significant differences in investigatory behaviors, levels of corticosterone, or activation of gonadotropin-releasing hormone-containing cells between the two groups. As has been reported previously, the levels of testosterone were lower in the aged rats. However, stimulus-induced neural activity was higher in the bed nucleus of the stria terminalis and the medial preoptic area of aged rats, whereas no differences were found in the main olfactory bulb, accessory olfactory bulb, medial amygdala, ventral tegmental area, or nucleus accumbens. These findings suggest the presence of a compensatory mechanism in the hypothalamus of aged animals versus adults, whereby more cells are recruited to elicit a sexual response in the presence of a sexually exciting stimulus.