Dietary L-tryptophan modulates agonistic behavior and brain serotonin in male dyadic contests of a cichlid fish.

Although some studies have investigated the effects of dietary L-tryptophan on agonistic behavior, research on adult fish specimens is still lacking. Moreover, submissive behaviors have been generally overlooked. We focused on agonistic behavior between males of the cichlid fish Cichlasoma dimerus, in dyadic encounters held in a novel context after being fed or not with an L-tryptophan enriched diet (TRP) for 2 weeks. We arranged three different dyads: control/control (control conditions: not TRP enriched), control/TRP, and TRP/TRP. We also registered the response of the brain serotonergic system in four brain regions. TRP/TRP dyads showed higher latencies to first attack, lower overall aggression, and lower proportions of bites and passive copings (submissive display) compared to control/control. TRP dominant males performed fewer bites with respect to controls, and subordinate males opposed to TRP males showed fewer passive copings. Higher serotonergic activities were found in subordinates' optic tectum and in the telencephalon and preoptic area/hypothalamus of TRP males. Altogether, results point out that dietary L-tryptophan reduced males' motivation to attack and dominant aggression, which consequently influenced subordinate agonistic repertory. In addition, males within TRP/TRP dyads showed a switch in their behavioral agonistic repertory. These behavioral outcomes were probably due to modifications at brain serotonergic functioning.

5-HT2B, 5-HT7, and DA2 Receptors Mediate the Effects of 5-HT and DA on Agonistic Behavior of the Chinese Mitten Crab (Eriocheir sinensis).

The Chinese mitten crab (Eriocheir sinensis) is a commercially important crab in China and is usually managed at high stocking densities. Agonistic behavior directly impacts crab integrity, survival, and growth and results in economic losses. In the present study, we evaluated the modulatory effects of serotonin (5-HT) and dopamine (DA) though the 5-HT2 and DA2 receptor-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway on agonistic behavior. The results showed that injection of either 10-6 mol/crab 5-HT or DA reduced the agonistic behavior of E. sinensis (P < 0.05), as did 10-10 mol/crab DA and 10-8 mol/crab 5-HT and DA (P < 0.05); however, a dose of 10-10 mol/crab 5-HT promoted agonistic behavior. 5-HT significantly increased the mRNA expression level of 5-HT7 receptor and reduced that of the DA2 receptor in the cerebral ganglion (P < 0.05). In contrast to 5-HT, DA significantly decreased 5-HT2B mRNA levels and increased 5-HT7 and DA2 receptor levels in the thoracic ganglia (P < 0.05). In addition, injections of either 5-HT or DA increased the cAMP and PKA levels in hemolymph (P < 0.05). By using in vitro culture of the thoracic ganglia, the current study showed that ketanserin (5-HT2 antagonist) and [R(-)-TNPA] (DA2 agonist) had obvious effects on the expression levels of the two receptors (P < 0.05). In vivo experiments further demonstrated that ketanserin and [R(-)-TNPA] could both significantly reduce the agonistic behavior of the crabs (P < 0.05). Furthermore, both ketanserin and [R(-)-TNPA] promoted the cAMP and PKA levels (P < 0.05). The injection of CPT-cAMP (cAMP analogue) elevated the PKA levels and inhibited agonistic behavior. In summary, this study showed that 5HT-2B and DA2 receptors were involved in the agonistic behavior that 5-HT/DA induced through the cAMP-PKA pathway in E. sinensis.

Field-testing a single-dose immunocontraceptive in free-ranging male capybara (Hydrochoerus hydrochaeris): Evaluation of effects on reproductive physiology, secondary sexual characteristics, and agonistic behavior.

Controlling wildlife populations to mitigate human-wildlife conflicts and the spread of zoonotic diseases is an ever-growing necessity. The objective of this study was to evaluate a single-dose anti-gonadotropin-releasing hormone vaccine (GonaCon, USDA/NWRC, Fort Collins, CO, USA) as a non-lethal alternative for population control in free-ranging, synanthropic male capybara. In addition to infertility efficacy of this treatment, potential effects on the alpha male's secondary sexual characteristics and agonist behavior need to be assessed because any alterations in these factors could lead to population management failure. The treatment group (n = 3) received 1 mL of the anti-GnRH vaccine, intramuscularly, and the control group (n = 2) a 1 mL sham vaccine. Reproductive behavior and social group dynamics were monitored for 30 days prior to inoculation (June 2017) with continuous observations occurring during the study period. Antifertility effects were assessed by conducting exams of testicular morphology, semen characteristics, and histological analysis (after 270 days via hemi-gonadectomy). Compared to the control group, the testicles of the treated males had severe atrophy (P <  0.05), oligozoospermia and greater numbers of sperm cells in a static developmental phase. Courtship and agonistic alpha male behavior were not altered, and the group's social integrity was maintained. Results indicate there was 100% infertility in capybara males, observed throughout the study period of 18 months, and equally important, the male's alpha characteristics were not affected by the treatment, which is imperative for successful capybara population control efforts.

Vasotocinergic control of agonistic behavior told by Neotropical fishes.

The hypothalamic neuropeptides of the vasopressin-oxytocin family (and their homologs for non-mammalian species) are key modulators of the Social Brain Network, acting via specific receptors reported in all the nuclei of this network. Different conclusive examples have proven the context-dependency actions of hypothalamic nonapeptides on social behavior in several vertebrate taxa. Teleost fishes provide endless possibilities of experimental model systems to explore the underlying mechanisms of nonapeptide actions on social behavior given that they are the most diverse group of vertebrates. Although it has been difficult to identify commonalities of nonapeptide actions across species, indisputable evidence in many teleost species have demonstrated a clear role of vasotocin in the modulation of aggressive and sexual behaviors. Though Neotropical South American fish contribute an important percentage of teleost diversity, most native species remain unexplored as model systems for the study of the neuroendocrine bases of social behavior. In this review, we will revise recent data on the two model systems of Neotropical fish, South American cichlids and weakly electric fish that have contributed to this issue.

A Conserved Role for Serotonergic Neurotransmission in Mediating Social Behavior in Octopus.

Human and octopus lineages are separated by over 500 million years of evolution [1, 2] and show divergent anatomical patterns of brain organization [3, 4]. Despite these differences, growing evidence suggests that ancient neurotransmitter systems are shared across vertebrate and invertebrate species and in many cases enable overlapping functions [5]. Sociality is widespread across the animal kingdom, with numerous examples in both invertebrate (e.g., bees, ants, termites, and shrimps) and vertebrate (e.g., fishes, birds, rodents, and primates) lineages [6]. Serotonin is an evolutionarily ancient molecule [7] that has been implicated in regulating both invertebrate [8] and vertebrate [9] social behaviors, raising the possibility that this neurotransmitter's prosocial functions may be conserved across evolution. Members of the order Octopoda are predominantly asocial and solitary [10]. Although at this time it is unknown whether serotonergic signaling systems are functionally conserved in octopuses, ethological studies indicate that agonistic behaviors are suspended during mating [11-13], suggesting that neural mechanisms subserving social behaviors exist in octopuses but are suppressed outside the reproductive period. Here we provide evidence that, as in humans, the phenethylamine (+/-)-3,4-methylendioxymethamphetamine (MDMA) enhances acute prosocial behaviors in Octopus bimaculoides. This finding is paralleled by the evolutionary conservation of the serotonin transporter (SERT, encoded by the Slc6A4 gene) binding site of MDMA in the O. bimaculoides genome. Taken together, these data provide evidence that the neural mechanisms subserving social behaviors exist in O. bimaculoides and indicate that the role of serotonergic neurotransmission in regulating social behaviors is evolutionarily conserved.

Prenatal bisphenol A exposure is associated with medial amygdala neuron hyperresponsiveness to predator odor in rats.

Perinatal exposure to bisphenol A (BPA) causes several alterations in brain function and behavior. In previous studies, we showed that prenatal treatment with low-level BPA impaired gender-specific behavior, enhanced depression-like behavior, and augmented behavioral responses to predator odor in rats. On this premise, we hypothesized that BPA-treated rats were more susceptible to predator odor stress. To test the potential neural mechanism underlying this effect, we conducted an electrophysiological study of neurons in the medial amygdala-a regional component of the olfactory pathway with high estrogen and androgen receptor expression, and thus a potential target of BPA-in rats exposed to BPA. Extracellular recordings were obtained during the presentation of 3 plant odors and 3 predator odorants. Odor-responsive neurons in BPA-exposed rats showed greater activity in response to fox odor than did those in control rats. This finding complements the results of our previous behavioral study in which BPA-exposed rats exhibited enhanced avoidance behavior in response to fox odor. Given the close relationship between olfactory signaling and the stress response system, we suspect that BPA modifies the olfactory pathway at the level of the medial amygdala and thus modulates the corresponding stress response.

Exposure to a nicotinoid pesticide reduces defensive behaviors in a non-target organism, the rusty crayfish Orconectes rusticus.

Imidacloprid is the most widely used of the nicotinoid insecticides, the fastest growing class of pesticides on the global market. Although less toxic to mammals and birds compared to organophosphates, nicotinoids have the potential to impact non-target invertebrates, especially through sublehal effects on behavior, physiology, reproduction, and development. We investigated the impact of sublethal doses of imidacloprid on the defensive responses of rusty crayfish Orconectes rusticus exposed to 0, 1, 10, and 100 µg•L-1 of imidacloprid for 10 days (n = 7 crayfish per treatment). Defensive behaviors were examined with the rod test, in which a glass rod was jabbed into the crayfish's container at a 90 degree angle from the bottom and about 0.5 cm directly in front of the crayfish. Crayfish responded to the rod aggressively with claw raising and pinching, neutrally (no response), or by backing or tail-flipping away. The frequency of neutral responses more than doubled after four days in the high (100 µg•L-1) group and after eight days in the low (1 µg•L-1) exposure group. Furthermore, most crayfish in the 100 µg•L-1 treatment were not able to right themselves within 30 s when placed on their backs. Several studies have reported concentrations of imidacloprid contamination in freshwater ecosystems that exceed this study's lowest exposure scenario, 1 µg•L-1. We therefore conclude that imidacloprid contamination reduces the defensive behaviors of crayfish, impairing their ability to survive in habitats where they play important ecological roles.

Clinical spectrum of KIAA2022 pathogenic variants in males: Case report of two boys with KIAA2022 pathogenic variants and review of the literature.

KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.

Tyraminergic modulation of agonistic outcomes in crayfish.

Octopamine, a biogenic amine, modulates various behaviors, ranging from locomotion and aggression to learning and memory in invertebrates. Several studies recently demonstrated that tyramine, the biological precursor of octopamine, also affects behaviors independent of octopamine. Here we investigated the involvement of tyramine in agonistic interaction of the male crayfish Procambarus clarkii. When male crayfish fight, larger animals (3-7% difference in body length) are more likely to win. By contrast, direct injection of tyramine or octopamine counteracted the physical advantage of larger animals. Tyramine or octopamine-injected naive large animals were mostly beaten by untreated smaller naive animals. This pharmacological effect was similar to the loser effect in which subordinate larger animals are frequently beaten by smaller animals. Furthermore, loser effects were partly eliminated by either injection of epinastine, an octopamine blocker, or yohimbine, a tyramine blocker, and significantly diminished by injection of a mixture of both blockers. We also observed that tyramine levels in the subesophageal ganglion were remarkably increased in subordinate crayfish after losing a fight. These results suggest that tyramine modulates aggressive levels of crayfish and contributes to the loser effect in parallel with octopamine.

Vasotocin increases dominance in the weakly electric fish Brachyhypopomus gauderio.

Animals establish social hierarchies through agonistic behavior. The recognition of the own and others social ranks is crucial for animals that live in groups to avoid costly constant conflicts. Weakly electric fish are valuable model systems for the study of agonistic behavior and its neuromodulation, given that they display conspicuous electrocommunication signals that are generated by a very well-known electromotor circuit. Brachyhypopomus gauderio is a gregarious electric fish, presents a polygynous breeding system, morphological and electrophysiological sexual dimorphism during the breeding season, and displays a typical intrasexual reproduction-related aggression. Dominants signal their social status by increasing their electric organ discharge (EOD) rate after an agonistic encounter (electric dominance). Subordinates only occasionally produce transient electric signals (chirps and offs). The hypothalamic neuropeptide arginine-vasotocin (AVT) and its mammalian homologue, arginine- vasopressin (AVP) are key modulators of social behavior across vertebrates. In this study, we focus on the role of AVT on dominance establishment in Brachyhypopomus gauderio by analyzing the effects of pharmacological manipulations of the AVT system in potential dominants. AVT exerts a very specific direct effect restricted only to EOD rate, and is responsible for the electric dominance. Unexpectedly, AVT did not affect the intensity of aggression in either contender. Nor was the time structure affected by AVT administration. We also present two interesting examples of the interplay between contenders by evaluating how AVT modulations, even when directed to one individual, affect the behavior of the dyad as a unit. First, we found that V1a AVT receptor antagonist Manning Compound (MC) induces a reversion in the positive correlation between dominants' and subordinates' attack rates, observed in both control and AVT treated dyads, suggesting that an endogenous AVT tone modulates aggressive interactions. Second, we confirmed that AVT administered to dominants induces an increase in the submissive transient electric signals in subordinates.

Social change and access to a palatable diet produces differences in reward neurochemistry and appetite in female monkeys.

Understanding factors that contribute to the etiology of obesity is critical for minimizing the effects of obesity-related adverse physical health outcomes. Emotional eating or the inability to control intake of calorically dense diets (CDD) under conditions of psychosocial stress exposure is a potential risk factor for the development of obesity in people. Decreases in dopamine 2 receptors (D2R) availability have been documented in substance abuse and obesity in humans, as well as animal models of chronic stressor exposure. Social subordination in macaques is a well-established animal model of a chronic psychogenic stressor that results in stress axis dysregulation, attenuated striatal D2R levels, and stress-induced hyperphagia in complex dietary environment. However, it remains unclear how these phenotypes emerge as the stressor becomes chronic during the formation of new social groups. Thus, the goal of the current study was to assess how the imposition of social subordination over a four-month period would affect food intake, socioemotional behavior, and D2R binding potential (D2R-BP) in female rhesus monkeys maintained on a typical laboratory chow diet (LCD) compared with those having a choice between a LCD and a CDD. Results showed that access to a CDD leads to increased total caloric intake and preference for a CDD over a LCD. For the dietary choice condition, females directing less aggression towards group mates during the four-month period, a characteristic of lower social status, consumed progressively more calories over the four-month period than more aggressive females. This relation between agonistic behavior and appetite was not observed for females in LCD-only condition. Finally, decreased D2R-BP in the orbitofrontal cortex was predictive of increased overall caloric intake in all females regardless of dietary environment, suggesting that reduced availability of D2R within the prefrontal cortex is associated with unrestrained eating. Studies are continuing to determine how newly imposed dominance ranks continue to affect reward neurochemistry and appetite over time, and how this is influenced by the dietary environment.

Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.

Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice.

UV-filter benzophenone-3 inhibits agonistic behavior in male Siamese fighting fish (Betta splendens).

Benzophenone-3 (BP-3) is a widely used organic UV-filter compound. Despite the frequent occurrence of BP-3 in aquatic environments, little is known about its effect on fish behavior. The aim of this study was to investigate the endocrine disrupting effects of BP-3 in male fighting fish (Betta splendens) with a focus on agonistic behavior. Male fighting fish were exposed to 10, 100, and 1000 µg/L BP-3, as well as a solvent control (0.1% ethanol) and a positive control (100 ng/L 17α-ethynylestradiol, EE2), for 28 days. At the beginning and the end of exposure, standard length and body mass of the fish were measured for calculating the condition factor (CF). In addition, spontaneous swimming activity (total distance moved) and agonistic behavior (maximum velocity and duration of opercular display in front of a mirror) were also quantified. At the end of exposure, the fish gonads were sampled for gonadosomatic index (GSI) measurement and histology. After the exposure, CF was significantly decreased in the 1000 µg/L BP-3 groups. Spontaneous swimming activity was not affected. However, maximum velocity was significantly reduced in the EE2 and 1000 µg/L BP-3 treatments; duration of opercular display was significantly decreased in the EE2 and 10 and 1000 µg/L BP-3 treatments. GSI was not significantly different between groups. There was a slight but statistically significant decrease of relative proportion of mature spermatozoa in testicular tissue in the 100 µg/L BP-3 treatment. Collectively, our results demonstrate that BP-3 can disrupt agonistic behavior of male fighting fish, indicating the endocrine disrupting activity of this compound.

Intranasally administered oxytocin affects how dogs (Canis familiaris) react to the threatening approach of their owner and an unfamiliar experimenter.

Fear and aggression are among the most prominent behavioural problems in dogs. Oxytocin has been shown to play a role in regulating social behaviours in humans including fear and aggression. As intranasal oxytocin has been found to have some analogous effects in dogs and humans, here we investigated the effect of oxytocin on dogs' behaviour in the Threatening Approach Test. Dogs, after having received intranasal administration of oxytocin (OT) or placebo (PL), showed the same reaction to an unfamiliar experimenter, but OT pretreated dogs showed a less friendly first reaction compared to the PL group when the owner was approaching. Individual differences in aggression (measured via questionnaire) also modulated dogs' first reaction. Moreover, subjects that received OT looked back more at the human (owner/experimenter) standing behind them during the threatening approach. These results suggest that oxytocin has an effect on dogs' response to the threatening cues of a human, but this effect is in interaction with other factors such as the identity of the approaching human and the 'baseline' aggression of the dogs.

Effects of Phenibut and Citrocard on Non-Competitive and Competitive Behavior during Provoked Aggression in Animals.

Anti-aggressive effects of phenibut (25 mg/kg) and its structural analogue citrocard (50 mg/kg) were revealed in rats under condition of provoked intraspecific aggression. These substances significantly decreased manifestations of aggression in animals: they increased the latency of attacks and reduced their number. Anti-aggressive effects of citrocard were more pronounced than effects of phenibut under conditions of non-competitive aggression induced by fear of inescapable painful exposure or under conditions of competitive aggression reflecting the ability of animals to reveal adaptive social communicative skills in aversive situation.

Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.

Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute social defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1mg/kg or 25mg/kg of cocaine. The effects of social defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25mg/kg. Adult mice exposed to social defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of social defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced.

Involvement of 2-arachidonoylglycerol signaling in social challenge responding of male CD1 mice.

RATIONALE: Endocannabinoids are strong modulators of emotionality and present a novel target for psychotropic drug development. Increasing evidence suggests that endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) affect behavior differentially. While the roles of anandamide have been investigated extensively, studies regarding the specific roles of 2-AG became possible only recently, and its involvement in social behaviors has not yet been studied. OBJECTIVE: We studied the impact of 2-AG signaling on aggression as a first attempt to characterize the role of this endocannabinoid in social behaviors. METHODS: 2-AG signaling was enhanced by the monoacylglycerol lipase inhibitor JZL184 (8, and 16 mg/kg) in mice later submitted to the resident/intruder paradigm. RESULTS: JZL184 near completely abolished aggressiveness in residents and increased victimization (i.e., attacks by the opponent). Interestingly, the level of defensiveness remained unaltered, despite the large increase in bites received. The CB1 receptor blocker AM251 (0.5 mg/kg) did not influence the effects of JZL184. In intruders, JZL184 near completely suppressed bites and offensive behavior in a fashion similar to residents, but it also increased agitation and defensiveness during, and the corticosterone response to, aggressive encounters. Experiments involving the corticosterone synthesis inhibitor metyrapone (30 mg/kg) suggest that the suppression of biting and offensive behavior is directly influenced by JZL184, whereas increased agitation and defensiveness (seen in intruders only) are a secondary development of the stress-endocrine effects of JZL184. CONCLUSIONS: 2-AG signaling emerges as a surprisingly strong negative modulator of aggressiveness, which warrants further studies into its general role in social behavior and the target receptors involved.

The antidepressant venlafaxine disrupts brain monoamine levels and neuroendocrine responses to stress in rainbow trout.

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is a widely prescribed antidepressant drug routinely detected in the aquatic environment. However, little is known about its impact on the physiology of nontarget organisms. We tested the hypothesis that venlafaxine perturbs brain monoamine levels and disrupts molecular responses essential for stress coping and feeding activity in fish. Rainbow trout (Oncorhynchus mykiss) were exposed to waterborne venlafaxine (0.2 and 1.0 µg/L) for 7 days. This treatment elevated norepinephrine, serotonin, and dopamine levels in the brain in a region-specific manner. Venlafaxine also increased the transcript levels of genes involved in stress and appetite regulation, including corticotropin releasing factor, pro-opiomelanocortin B, and glucose transporter type 2 in distinct brain regions of trout. The drug treatment reduced the total feed consumed per day, but did not affect the feeding behavior of the dominant and subordinate fish. However, the subordinate fish from the venlafaxine-exposed group had significantly higher plasma cortisol levels compared to the subordinate fish in the control group. Collectively, our results demonstrate that venlafaxine, at environmentally realistic levels, is a neuroendocrine disruptor, impacting the stress and feeding responses in rainbow trout. We propose the midbrain region as a key target for venlafaxine impact and the mode of action involves abnormal monoamine content in trout.

Decreased allopregnanolone induced by hormonal contraceptives is associated with a reduction in social behavior and sexual motivation in female rats.

RATIONALE: Allopregnanolone is a neurosteroid involved in depression, memory, social, and sexual behavior. We have previously demonstrated that treatment with a combination of ethinylestradiol (EE) and levonorgestrel (LNG), two compounds frequently used in hormonal contraception, decreased brain allopregnanolone concentrations. These changes may contribute to some of the emotional and sexual disorders observed in hormonal contraceptive users. OBJECTIVES: We thus examined whether the reduction in allopregnanolone concentrations induced by long-term EE/LNG administration was associated with altered emotional, learning, social, and sexual behaviors. METHODS: Rats were orally treated with a combination of EE (0.030 mg) and LNG (0.125 mg) once a day for 4 weeks and were subjected to behavioral tests 24 h after the last administration. RESULTS: EE/LNG treatment reduced immobility behavior in the forced swim test, without affecting sucrose preference and spatial learning and memory. In the resident-intruder test, EE/LNG-treated rats displayed a decrease in dominant behaviors associated with a reduction in social investigation. In the paced mating test, EE/LNG treated rats showed a reduction in proceptive behaviors, while the lordosis quotient was not affected. Progesterone, but not estradiol, administration to EE/LNG-treated rats increased sexual activity and cerebrocortical allopregnanolone concentrations. Prior administration of finasteride decreased allopregnanolone concentrations and abolished the increase in proceptivity induced by progesterone administration. CONCLUSIONS: The decrease in brain allopregnanolone concentrations induced by EE/LNG treatment is associated with a reduction in social behavior and sexual motivation in female rats. These results might be relevant to the side effects sometimes exhibited by women taking hormonal contraceptives.

Contextual modulation of androgen effects on agonistic interactions.

Seasonal changes in steroid hormones are known to have a major impact on social behavior, but often are quite sensitive to environmental context. In the bi-directionally sex changing fish, Lythrypnus dalli, stable haremic groups exhibit baseline levels of interaction. Status instability follows immediately after male removal, causing transiently elevated agonistic interactions and increase in brain and systemic levels of a potent fish androgen, 11-ketotestosterone (KT). Coupling KT implants with a socially inhibitory environment for protogynous sex change induces rapid transition to male morphology, but no significant change in social behavior and status, which could result from systemically administered steroids not effectively penetrating into brain or other tissues. Here, we first determined the degree to which exogenously administered steroids affect the steroid load within tissues. Second, we examined whether coupling a social environment permissive to sex change would influence KT effects on agonistic behavior. We implanted cholesterol (Chol, control) or KT in the dominant individual (alpha) undergoing sex change (on d0) and determined the effects on behavior and the degree to which administered steroids altered the steroid load within tissues. During the period of social instability, there were rapid (within 2 h), but transient effects of KT on agonistic behavior in alphas, and secondary effects on betas. On d3 and d5, all KT, but no Chol, treated females had male typical genital papillae. Despite elevated brain and systemic KT 5 days after implant, overall rates of aggressive behavior remained unaffected. These data highlight the importance of social context in mediating complex hormone-behavior relationships.