Centrally released oxytocin mediates mating-induced anxiolysis in male rats

Abstract

Sexual activity and mating are accompanied by a high level of arousal, whereas anecdotal and experimental evidence demonstrate that sedation and calmness are common phenomena in the postcoital period in humans. These remarkable behavioral consequences of sexual activity contribute to a general feeling of well being, but underlying neurobiological mechanisms are largely unknown. Here, we demonstrate that sexual activity and mating with a receptive female reduce the level of anxiety and increase risk-taking behavior in male rats for several hours. The neuropeptide oxytocin has been shown to exert multiple functions in male and female reproduction, and to play a key role in the regulation of emotionality after its peripheral and central release, respectively. In the present study, we reveal that oxytocin is released within the brain, specifically within the hypothalamic paraventricular nucleus, of male rats during mating with a receptive female. Furthermore, blockade of the activated brain oxytocin system by central administration of an oxytocin receptor antagonist immediately after mating prevents the anxiolytic effect of mating, while having no effect in nonmated males. These findings provide direct evidence for an essential role of an activated brain oxytocin system mediating the anxiolytic effect of mating in males.black-white box ͉ elevated plus maze ͉ paraventricular nucleus ͉ risk-taking behavior ͉ anxiety T he neuropeptide oxytocin (OT) is a well acknowledged neuromodulator/neurotransmitter of the brain regulating emotionality, stress coping, and prosocial behaviors (1-3). In females, high activity of the brain OT system has been linked to the fine-tuned regulation of parturition and milk letdown (4), to the performance of maternal behaviors (3), and to the low stress response characteristic for the peripartum period (5, 6). Importantly, behavioral and physiological actions of intracerebral OT are not limited to females, because OT synthesis, local OT release, and OT receptor binding have also been demonstrated in the male brain (2, 7, 8). A major site of both OT synthesis and release within the brain is the hypothalamic paraventricular nucleus (PVN) (2), a region integrating behavioral and neuroendocrine stress responses (9). In male rats and mice, OT is an important regulator of sexual function (10), of anxiety (11), and of stress-coping circuitries (12)(13)(14). Moreover, in humans, intranasal OT was recently described to promote trust (15), and to reduce the level of anxiety (16), possibly at the level of the amygdala (17). With respect to sexual activity, preclinical (18) and human (19) research has shown elevated OT secretion into the blood during mating behavior and orgasm, respectively. Additionally, increased OT levels have been described in the cerebrospinal fluid after mating in rats (20), which is indicative of stimulation of the OT system (21).In combination, these findings lead us to hypothesize that mating results in reduced anxiety-related behavior, possibly mediated by an elevation in local...

Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking

“…This could result in impaired discrimination between familiar and unfamiliar female odor, thus, modifying sexual motivation. This is supported by the findings that exposure to the signals of an estrous female results in the activation of brain OT at the level of the paraventricular nucleus of the hypothalamus (Waldherr and Neumann, 2007). Moreover, this OT activation was associated with an anxiolytic response and reduced emotional response to anxiogenic stimuli that is consistent with an enhanced risk taking and boldness.…”

Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice

“…Adult Oxtr Ϫ/Ϫ males show a deficit in social discrimination and an increase in aggressive behavior (Takayanagi et al, 2005). OXT has also been shown to mediate mating-induced anxiolysis in male rat (Waldherr and Neumann, 2007). However, the cellular mechanisms by which the OX-T-OXTR system modulates social and emotional behavior remain unknown.…”

“…In the brain, the OXTR is abundantly present in several brain regions (i.e., some cortical areas, the olfactory system, the basal ganglia, the limbic system, the thalamus, the hypothalamus, the brainstem, and the spinal cord) (Yoshimura et al, 1993;Vaccari et al, 1998;Gimpl and Fahrenholz, 2001), suggesting that the OXTR in the CNS has a wide variety of effects. In addition to its classical functions (i.e., induction of labor and milk ejection), OXT plays an important role in regulating social behaviors, anxiety-related behaviors, food intake, stress-related responses, and pain control (Ferguson et al, 2000;Gimpl and Fahrenholz, 2001;Takayanagi et al, 2005;Waldherr and Neumann, 2007).…”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…Oxytocin's actions in the brain reduce stress-induced corticosterone release and anxiety behavior in rodents 210 and oxytocin was also shown to be a key player in the social buffering of stress. Oxytocin release within the paraventricular nucleus of the hypothalamus, triggered by mating, mediated mating-induced anxiolytic behavior in male rats 211 . Oxytocin release that was independent of mating was involved in the buffering of stress-induced increases in anxiety-like behaviors and circulating corticosterone that occur in female prairie voles if the male partner is present 212 .…”