Sex-dependent effects of social status on the regulation of arginine-vasopressin (AVP) V1a, oxytocin (OT), and serotonin (5-HT) 1A receptor binding and aggression in Syrian hamsters (Mesocricetus auratus).

Dominance status in hamsters is driven by interactions between arginine-vasopressin V1a, oxytocin (OT), and serotonin 1A (5-HT1A) receptors. Activation of V1a and OT receptors in the anterior hypothalamus (AH) increases aggression in males, while decreasing aggression in females. In contrast, activation of 5-HT1A receptors in the AH decreases aggression in males and increases aggression in females. The mechanism underlying these differences is not known. The purpose of this study was to determine if dominance status and sex interact to regulate V1a, OT, and 5-HT1A receptor binding. Same-sex hamsters (N = 47) were paired 12 times across six days in five min sessions. Brains from paired and unpaired (non-social control) hamsters were collected immediately after the last interaction and processed for receptor binding using autoradiography. Differences in V1a, OT, and 5-HT1A receptor binding densities were observed in several brain regions as a function of social status and sex. For example, in the AH, there was an interaction between sex and social status, such that V1a binding in subordinate males was lower than in subordinate females and V1a receptor density in dominant males was higher than in dominant females. There was also an interaction in 5-HT1A receptor binding, such that social pairing increased 5-HT1A binding in the AH of males but decreased 5-HT1A binding in females compared with unpaired controls. These results indicate that dominance status and sex play important roles in shaping the binding profiles of key receptor subtypes across the neural circuitry that regulates social behavior.

Arginine-vasopressin and the regulation of aggression in female Syrian hamsters (Mesocricetus auratus).

Arginine-vasopressin (AVP) is critical for the expression of a variety of social behaviors in many species. Previous studies have demonstrated that AVP regulates behaviors such as social communication and aggression in Syrian hamsters through the V1a receptor subtype. In male hamsters, AVP injected into the anterior hypothalamus (AH) stimulates aggression, while injection of a V1a receptor antagonist inhibits the behavior. The purpose of the present studies was to determine whether AVP influences aggression by its action in the AH in female hamsters. In the first experiment, we were surprised to find that injection of the V1a receptor antagonist, Manning compound, into the AH of intact female hamsters increased aggression. The second experiment confirmed the ability of the V1a receptor antagonist to increase aggression and found that the largest effects of the antagonist occurred at intermediate concentrations of the compound. The next experiment found that injection of AVP into the AH significantly reduced the latency to attack and the duration of aggression. Finally, we examined whether the effects of AVP and the V1a receptor antagonist on aggression differed in hamsters exposed to long 'summer-like' photoperiods or short 'winter-like' photoperiods, and found that their effects on aggression were not photoperiod dependent. In summary, contrary to what is observed in males, these data suggest that AVP in the AH may play an inhibitory role on aggression in female Syrian hamsters.

Role for the NR2B subunit of the N-methyl-D-aspartate receptor in mediating light input to the circadian system.

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells that utilize glutamate as a neurotransmitter. A variety of evidence suggests that the release of glutamate then activates N-methyl-D-aspartate (NMDA) receptors within the SCN and triggers a signaling cascade that ultimately leads to phase shifts in the circadian system. In this study, we first sought to explore the role of the NR2B subunit in mediating the effects of light on the circadian system of hamsters and mice. We found that localized microinjection of the NR2B subunit antagonist ifenprodil into the SCN region reduces the magnitude of light-induced phase shifts of the circadian rhythm in wheel-running activity. Next, we found that the NR2B message and levels of phospho-NR2B vary with time of day in SCN tissue using semiquantitative real-time polymerase chain reaction and western blot analysis, respectively. Functionally, we found that blocking the NR2B subunit with ifenprodil significantly reduced the magnitude of NMDA currents recorded in SCN neurons. Ifenprodil also significantly reduced the magnitude of NMDA-induced Ca2+ changes in SCN cells. Together, these results demonstrate that the NR2B subunit is an important component of NMDA receptor-mediated responses within SCN neurons and that this subunit contributes to light-induced phase shifts of the mammalian circadian system.

GABA(B) receptor activation in the suprachiasmatic nucleus of diurnal and nocturnal rodents.

Diurnal (day-active) and nocturnal (night-active) animals have very different daily activity patterns. We recently demonstrated that the suprachiasmatic nucleus (SCN) responds to GABAergic stimulation differently in diurnal and nocturnal animals. Specifically, GABAA receptor activation with muscimol during the subjective day causes phase delays in diurnal grass rats while producing phase advances in nocturnal hamsters. The aim of the following experiments was to determine if diurnal and nocturnal animals differ in their response to GABAB receptor activation in the SCN. Baclofen, a GABAB receptor agonist, was microinjected into the SCN region of grass rats or hamsters under free-running conditions and phase alterations were analyzed. Changes in phase were not detected after baclofen treatment during the subjective day in either grass rats or hamsters. During the night, however, GABAB receptor activation significantly decreased the ability of light to induce phase delays in grass rats. Taken together with previous data from our laboratory, these results demonstrate that, in both hamsters and grass rats, GABAB receptor activation in the SCN significantly affects circadian phase during the night, but not during the day.

Neuropeptide Y and N-methyl-D-aspartic acid interact within the suprachiasmatic nuclei to alter circadian phase.

Circadian rhythms are reset by exposure to photic stimuli and nonphotic stimuli. Glutamate appears to be the primary neurotransmitter that communicates photic stimuli to the circadian clock located in the suprachiasmatic nucleus. There is also substantial evidence that neuropeptide Y (NPY) mediates the effects of at least some nonphotic stimuli on the circadian clock. The purpose of this study was to investigate how NPY and glutamate receptor activation interact to reset the phase of the circadian clock. Microinjection of the glutamate agonist N-methyl-D-aspartic acid (NMDA) during the subjective day significantly decreased NPY-induced phase advances. During the late subjective night, NMDA induced light-like phase advances, which were significantly reduced by microinjection of NPY. Microinjection of NPY inhibited NMDA-induced phase advances during the late subjective night, even when sodium-dependent action potentials were inhibited by tetrodotoxin. These data support the hypothesis that, during the subjective night, NPY and NMDA act on the same clock cells or on cells that communicate with clock cells by mechanisms not requiring action potentials. Although NPY and NMDA appear to be mutually inhibitory during both the day and the night, the mechanisms of this inhibition appear to be different during the day versus the night.

Novel phase-shifting effects of GABAA receptor activation in the suprachiasmatic nucleus of a diurnal rodent.

The vast majority of neurons in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, contain the inhibitory neurotransmitter GABA. Most studies investigating the role of GABA in the SCN have been performed using nocturnal rodents. Activation of GABA(A) receptors by microinjection of muscimol into the SCN phase advances the circadian activity rhythm of nocturnal rodents, but only during the subjective day. Nonphotic stimuli that reset the circadian pacemaker of nocturnal rodents also produce phase advances during the subjective day. The role of GABA in the SCN of diurnal animals and how it may differ from nocturnal animals is not known. In the studies described here, the GABA(A) agonist muscimol was microinjected directly into the SCN region of diurnal unstriped Nile grass rats (Arvicanthis niloticus) at various times in their circadian cycle. The results demonstrate that GABA(A) receptor activation produces large phase delays during the subjective day in grass rats. Treatment with TTX did not affect the ability of muscimol to induce phase delays, suggesting that muscimol acts directly on pacemaker cells within the SCN. These data suggest that the circadian pacemakers of nocturnal and diurnal animals respond to the most abundant neurochemical signal found in SCN neurons in opposite ways. These findings are the first to demonstrate a fundamental difference in the functioning of circadian pacemaker cells in diurnal and nocturnal animals.

Short-photoperiod exposure reduces vasopressin (V1a) receptor binding but not arginine-vasopressin-induced flank marking in male Syrian hamsters.

In Syrian hamsters, socially relevant information is communicated with a form of scent marking known as flank marking. There is substantial evidence that arginine-vasopressin acting on V1a vasopressin receptors (V1aR) in the medial preoptic-anterior hypothalamic continuum (MPOA-AH) regulates the expression of flank marking. Previous studies have shown that the expression of flank marking is also influenced by the circulating concentrations of gonadal hormones. In hamsters housed in long 'summer-like' photoperiods (i.e. >12.5 h of light/day), castration reduces flank marking and administration of testosterone restores precastration levels of flank marking. When exposed to short 'winter-like' photoperiods (i.e. <12.5 h of light/day), hamsters undergo gonadal regression and the circulating levels of testosterone decline. Surprisingly, flank marking induced during social encounters is not reduced in hamsters exposed to short photoperiods despite the low circulating concentrations of testosterone. In the present study, it was hypothesized that reductions in testosterone, caused by exposure to short photoperiod, would not reduce the ability of vasopressin to stimulate flank marking by its actions in the MPOA-AH. The amount of flank marking induced by vasopressin injected into the MPOA-AH did not significantly differ between hamsters housed in long and short photoperiods; however, short photoperiod-exposed males had significantly less V1aR binding in the MPOA than long photoperiod-exposed males. These results support the hypothesis that the sensitivity of the MPOA-AH to vasopressin is not reduced in short photoperiod-exposed males, despite decreases in serum testosterone. However, by contrast to our predictions, short photoperiod-exposed males have significantly reduced V1aR binding in the MPOA-AH compared to long photoperiod-exposed males.

Transduction of light in the suprachiasmatic nucleus: evidence for two different neurochemical cascades regulating the levels of Per1 mRNA and pineal melatonin.

The suprachiasmatic nucleus (SCN) contains a circadian clock and regulates melatonin synthesis in the pineal gland. Light exposure during the subjective night acutely increases the mRNA levels of the Period (Per)1 gene in the SCN and acutely suppresses melatonin levels in the pineal gland. Activation of N-methyl-D-aspartate (NMDA) receptors in the SCN has been demonstrated to phase-shift the circadian clock in a manner similar to light. We tested the hypothesis that activation of excitatory amino acid (EAA) receptors in the SCN mediates the acute effects of light on Per1 mRNA levels and pineal melatonin. NMDA, injected into the SCN of Syrian hamsters during the night, acutely suppressed melatonin levels in the pineal gland. Both the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) and the alpha-amino-3-hydroxy-5-methylisoxazoleproprionic acid (AMPA)/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) inhibited the light-induced increase of Per1 mRNA levels in the SCN. In the same animals, however, these antagonists had no effect on the ability of light to suppress pineal melatonin. These results support the hypothesis that EAA receptor activation in the SCN is necessary for the acute effects of light on Per1 mRNA levels. They also indicate that NMDA receptor activation in the SCN is sufficient but may not be necessary for the acute effects of light on pineal melatonin. These data suggest that there may be at least two different neurochemical cascades that transduce the effects of light in the SCN

Oxytocin inhibits aggression in female Syrian hamsters.

Dominant subordinate relationships are formed as the result of social conflict and are maintained at least in part by communication. At this time, little is known about the neural mechanisms that are responsible for coordinating the social behaviours (e.g. aggression) that occur in association with the formation and maintenance of these relationships. The purpose of the present study was to investigate the role of oxytocin (OXT) within the medial preoptic anterior hypothalamic continuum (MPOA-AH) in the control of aggression in female hamsters. OXT injected into the MPOA-AH immediately before testing significantly reduced the duration of aggression in a dose-dependent manner. Injection of an OXT antagonist 30 min before testing significantly increased the duration of aggression. In contrast, the duration of aggression was not altered when hamsters were tested either 30 min after injection of OXT or immediately following injection of an OXT-antagonist. These data support the hypothesis that OXT release within the MPOA-AH regulates social behaviours important in the formation and maintenance of dominant subordinate relationships in female hamsters.

Social experience and social context alter the behavioral response to centrally administered oxytocin in female Syrian hamsters.

The type of social behavior displayed by an individual is profoundly influenced by its immediate social environment or context and its prior social experience. Although oxytocin is important in the expression of social behavior in several species, it is not known if social factors alter the ability of oxytocin to influence behavior. The purpose of the present study was to test the hypothesis that social experience and social context alter the ability of oxytocin to regulate flank marking (a form of scent marking) in female Syrian hamsters. Oxytocin was microinjected into the medial preoptic anterior hypothalamic continuum (MPOA-AH) of socially experienced, dominant female hamsters which were then tested with either a subordinate partner, with a novel partner, or alone. Oxytocin induced flank marking in a dose-dependent manner but only when the experienced dominant hamsters were tested with their familiar, subordinate partners. Oxytocin did not induce flank marking when injected into socially naive female hamsters that were tested with an opponent or alone. In males, by contrast, oxytocin induced flank marking in dominant hamsters when they were tested with their subordinate partner or alone. These data support the hypothesis that social experience and social context interact to regulate the ability of oxytocin to stimulate flank marking by its actions in the MPOA-AH in female hamsters.

GABA interacts with photic signaling in the suprachiasmatic nucleus to regulate circadian phase shifts.

Circadian rhythms of physiology and behavior in mammals are driven by a circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. The majority of neurons in the suprachiasmatic nucleus are GABAergic, and activation of GABA receptors in the suprachiasmatic nucleus can induce phase shifts of the circadian pacemaker both in vivo and in vitro. GABA also modulates the phase shifts induced by light in vivo, and photic information is thought to be conveyed to the suprachiasmatic nucleus by glutamate. In the present study, we examined the interactions between GABA receptor agonists, glutamate agonists, and light in hamsters in vivo. The GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen were microinjected into the suprachiasmatic nucleus at circadian time 13.5 (early subjective night), followed immediately by a microinjection of N-methyl-D-aspartate (NMDA). Both muscimol and baclofen significantly reduced the phase shifting effects of NMDA. Further, coadministration of tetrodotoxin with baclofen did not alter the inhibition of NMDA by baclofen, suggesting a postsynaptic mechanism for the inhibition of NMDA-induced phase shifts by baclofen. Finally, the phase shifting effects of microinjection of muscimol into the suprachiasmatic nucleus during the subjective day were blocked by a subsequent light pulse. These data suggest that GABA regulates the phase of the circadian clock through both pre- and postsynaptic mechanisms.

The effects of endomorphin-1 on conditioned defeat in Syrian hamsters (Mesocricetus auratus).

The present study examined the effect of endomorphin-1 (EM1), an endogenous opioid with a high affinity for the mu opiate receptor, on conditioned defeat. Conditioned defeat is a phenomenon in which hamsters that have been defeated subsequently fail to exhibit normal territorial aggression and instead display submissive/defensive behaviors even when paired with a non-aggressive intruder. In experiment 1, animals were placed in the home cage of a larger resident for 15 min and were defeated. After 24 h, animals received a 3-microl injection of EM1 (0.0, 0.3, 3.0, or 10 nmol) into the left lateral cerebral ventricle 5 min before a smaller non-aggressive intruder was placed in the home cage of the experimental animal. In experiment 2, animals were infused with EM1 immediately after the initial defeat and were paired with a non-aggressive intruder 24 h later as in experiment 1. EM1 reduced the duration of submissive/defensive behavior in experiment 1 (P<0.05) but not in experiment 2 (P>0.05). These data support the hypothesis that the highly selective mu receptor agonist endomorphin-1 modulates the expression of conditioned defeat, but provides no support for the hypothesis that endomorphin-1 modulates the consolidation of conditioned defeat.

Distribution of hypocretin-(orexin) immunoreactivity in the central nervous system of Syrian hamsters (Mesocricetus auratus).

The hypocretins are peptides synthesized in neurons of the hypothalamus. Recent studies have suggested a role for these peptides in the regulation of sleep, feeding, and endocrine regulation. The distribution of hypocretin-immunoreactive cell bodies and fibers has been extensively described in rats, but not in other species. This study was designed to examine the distribution of hypocretin immunoreactivity in Syrian hamsters, as important differences in neuropeptide distribution between rats and hamsters have previously been demonstrated. Immunoreactive cell bodies were found primarily in the lateral hypothalamic area and the perifornical area, although a few hypocretin-positive cells were also located in the dorsomedial hypothalamus and the retrochiasmatic area. Fibers were distributed throughout the brain in a pattern similar to that seen in rats. The densest projections were found in the paraventricular nucleus of the thalamus, locus coeruleus, dorsal raphe, and lateroanterior hypothalamus. The innervation of the anterior hypothalamus may be of particular interest as similar cluster of immunoreactivity does not appear to be present in rats. Moderate levels of immunoreactivity could be seen throughout the hypothalamus, the lateral septum, bed nucleus of the stria terminalis, A5 noradrenergic area, and the midline thalamic nuclei. Hypocretin-immunoreactive fibers are present in all lamina of the spinal cord, with the greatest axon densities in lamina 1 and 10. The widespread distribution of hypocretin suggests its involvement in a wide variety of physiological and behavioral processes. Our results in hamsters indicate that the organization of the hypocretin system is strongly conserved across species, suggesting an important role for the peptide and its projections.

Endomorphin1-like immunoreactivity in the limbic system of Syrian hamsters (Mesocricetus auratus).

Recently, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2; EM1), an endogenous peptide that has high affinity and selectivity for the mu-opiate receptor, has been shown to modulate emotional behavior in mice and social behavior in Syrian hamsters. Endomorphin-1 (EM1) is present throughout the central nervous system in rats, mice, and guinea pigs; however, the distribution of EM1 in hamsters has not been described. The purpose of the present study was to investigate the distribution of EM1-like immunoreactivity (EM1L-IR) in the limbic system of Syrian hamsters using immunocytochemistry. Perikarya containing EM1L-IR were present in the anterior area, dorsomedial, ventromedial, periventricular, posterior, and arcuate nuclei of the hypothalamus. Fibers expressing EM1L-IR were present in the nucleus accumbens, caudate putamen, septum, bed nucleus of the stria terminalis, amygdaloid complex, and hypothalamus. The distribution of EM1 suggests a potential endogenous role for this peptide in major processes modulated by opiates, including affective states and social behavior.

Vasopressin (V1a) receptor binding, mRNA expression and transcriptional regulation by androgen in the Syrian hamster brain.

Arginine vasopressin plays an important role in the regulation of social behaviours in rodents. In the Syrian hamster, vasopressin injected directly into the brain stimulates scent marking and aggressive behaviour in a steroid dependent manner and is therefore a useful model for investigating steroid-peptide-behaviour interactions. In this study, we used in situ hybridization and radioligand binding assays on adjacent sections of hamster brains to compare the relative distribution of vasopressin (V1a) receptor mRNA and V1a receptor binding. V1a receptor mRNA and binding are abundant in the lateral septum, bed nucleus of the stria terminalis, medial preoptic nucleus, anterodorsal thalamus and suprachiasmatic nucleus. Moderate receptor binding and low levels of receptor mRNA are present in the central nucleus of the amygdala and a lateral zone from the medial preoptic area through the anterior hypothalamus. V1a receptor mRNA is anatomically more restricted in several areas compared to the ligand binding pattern, which is consistent with significant spread of receptor protein along neuronal processes. Comparison of V1a receptor ligand binding and mRNA in intact, castrated, and castrated-testosterone treated animals reveals that V1a receptors in the medial preoptic nucleus are regulated by androgen, most likely by an upregulation of V1a receptor gene expression in a cluster of neurones concentrated in the ventromedial part of this nucleus. This study confirms the presence of the V1a subtype of vasopressin receptors in behaviourally important regions of the hamster brain and suggests that transcriptional regulation by gonadal steroids may play a role in modulating behavioural sensitivity to vasopressin.

Conversion of testosterone to estradiol may not be necessary for the expression of mating behavior in male Syrian hamsters (Mesocricetus auratus).

Male sexual behavior is mediated in part by androgens, but in several species, mating is also influenced by estradiol formed locally in the brain by the aromatization of testosterone. The role of testosterone aromatization in the copulatory behavior of male Syrian hamsters is unclear because prior studies are equivocal. Therefore, the present study tested whether blocking the conversion of testosterone to estradiol would inhibit male hamster sexual behavior. Chronic systemic administration of the nonsteroidal aromatase inhibitor Fadrozole (2.0 mg/kg/day) for 5 or 8 weeks did not significantly increase mount latency or reduce mount frequency, intromission frequency, ejaculation frequency, or anogenital investigation relative to levels shown by surgical controls. However, Fadrozole effectively inhibited aromatase activity, as evidenced by the suppression of estrogen-dependent progesterone receptor immunoreactivity in the male hamster brain. The JZB39 anti-progesterone receptor antibody labeled significantly more neurons in brains of sham-treated hamsters than in brains of Fadrozole-treated hamsters. These data suggest that aromatization of testosterone to estradiol is not necessary for normal mating behavior in Syrian hamsters.

GABAergic regulation of light-induced c-Fos immunoreactivity within the suprachiasmatic nucleus.

Analysis of the photic induction of c-Fos immunoreactivity (-ir) within the suprachiasmatic nucleus (SCN) has proven to be a powerful tool with which to study the neurochemical mechanisms involved in phase shifting the circadian clock. Some systemically administered GABAergic drugs inhibit light-induced phase shifts and c-Fos-ir, whereas others inhibit light-induced phase shifts without affecting c-Fos-ir. More recently, we have found that injection of GABAergic drugs directly into the SCN region can have dramatically different effects on light-induced phase shifts than following their systemic administration. The present study investigated the effects of GABA(A) and GABA(B) agonists and antagonists injected into the SCN region on c-Fos-ir within the SCN. Microinjection of either a GABA(A) agonist, muscimol, or a GABA(B) agonist, baclofen, into the SCN region significantly reduced light-induced c-Fos-ir within the SCN when administered before light exposure at circadian time (CT) 13.5 or CT 19. In contrast, microinjection of a GABA(A) antagonist, bicuculline, but not a GABA(B) antagonist, CGP-35348, into the SCN region increased light-induced c-Fos-ir within the SCN when administered before light exposure at CT 13.5 or CT 19. These data indicate that GABAergic agonists and antagonists injected directly into the SCN region alter light-induced Fos-ir in a manner similar to their effects on light-induced phase shifts. Comparison of these data with previous studies examining the effects of systemically administered GABAergic drugs suggests that GABA(B)-active drugs have similar effects whether given systemically or within the SCN, but that GABA(A)-active drugs have more complex effects on c-fos induction and have multiple sites of action.

Activation of NMDA receptors in the suprachiasmatic nucleus produces light-like phase shifts of the circadian clock in vivo.

Although there is substantial evidence that glutamate mimics the effects of light on the mammalian circadian clock in vitro, it has been reported that microinjection of glutamate into the suprachiasmatic nucleus of the hypothalamus (SCN) region in vivo does not result in a pattern of phase shifts that mimic those caused by light pulses. The present study was designed to test the hypothesis that microinjection of NMDA into the SCN would induce light-like phase shifts of the circadian clock through activation of the NMDA receptor. Hamsters housed in constant darkness received microinjections of NMDA through guide cannulas aimed at the SCN region at various times throughout the circadian cycle. Wheel running was monitored as a measure of circadian phase. Microinjection of NMDA resulted in circadian phase shifts, the size and direction of which were dependent on the time of injection. The resulting phase-response curve closely resembled that of light. The circadian response showed a clear dose-dependence at circadian time (CT) 13.5 but not at CT19. Both phase delays and advances induced by NMDA were blocked by coinjection of the NMDA antagonist 2-amino-5-phosphopentanoic acid but were slightly attenuated by the non-NMDA antagonist 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione disodium. The ability of NMDA to induce phase shifts was not altered by coinjection with tetrodotoxin. These data are consistent with the hypothesis that activation of NMDA receptors is a critical step in the transmission of photic information to the SCN.

Glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus of rats housed in constant darkness.

This study demonstrates that the levels of the mRNAs encoding the two isoforms of glutamic acid decarboxylase (GAD) (i.e., GAD65 and GAD67) do not differ over the circadian activity cycle in the suprachiasmatic nucleus (SCN) of rats housed in constant darkness. These data indicate that the rhythmic expression of GAD56 mRNA previously observed in animals housed in a light:dark cycle [K.L. Huhman, A.C. Hennessey, H.E. Albers, Rhythms of glutamic acid decarboxylase mRNA in the suprachiasmatic nucleus, J. Biol. Rhythms 11 (1996) 311-316.] is the result of the activity of retinal afferents.

Injection of oxytocin into the medial preoptic-anterior hypothalamus increases ultrasound production by female hamsters.

Recent studies of hamsters have documented the facilitation of lordosis and other sociosexual responses by injections of oxytocin (OXT) into the medial preoptic area-anterior hypothalamus (MPOA-AH). These data suggest the regulation of social interaction and bonds by OXT. In turn, this suggests that OXT could act in the MPOA-AH to control other behaviors involved in the initiation or maintenance of social contact, including the ultrasonic vocalizations that female hamsters use to alert and attract potential mates. To test this possibility, we compared the ultrasound rates of 11 naturally estrous hamsters before and after injections of OXT (200 ng/200 nl of saline) or saline (200 nl) into the MPOA-AH. The data revealed a clear facilitation of ultrasound rate 30 min after OXT treatment. This result suggests the modulation of ultrasound rate by endogenous OXT acting within the MPOA-AH. It extends the range of social behaviors sensitive to control by OXT and supports the possibility that OXT acts within the MPOA-AH to facilitate a variety of behaviors involved in the establishment or maintenance of the social interactions required for successful reproduction. At the same time, these data extend earlier observations linking ultrasound production to the MPOA-AH, and begin to describe the peptidergic mechanisms controlling this form of reproductive behavior.