Oxytocin injected into the ventral subiculum or the posteromedial cortical nucleus of the amygdala induces penile erection and increases extracellular dopamine levels in the nucleus accumbens of male rats

Abstract

Oxytocin (20-100 ng) was found to be able to induce penile erection when injected unilaterally into the ventral subiculum or the posteromedial cortical nucleus of the amygdala of male rats. The pro-erectile effect started mostly 30 min after treatment and was abolished by the prior injection of d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (1-2 microg), an oxytocin receptor antagonist, into the ventral subiculum or posteromedial cortical nucleus. Oxytocin-induced penile erection occurred 15 min after the increase in the concentration of extracellular dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the dialysate obtained from the nucleus accumbens, which was also abolished by d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin. The pro-erectile effect of oxytocin was also reduced by cis-flupentixol (2 and 5 microg), a dopamine receptor antagonist, injected into the nucleus accumbens, and by (+)MK-801 (5 microg), a noncompetitive N-methyl-d-aspartate receptor antagonist, injected into the ventral tegmental area, but not into the nucleus accumbens. Together with studies showing that glutamatergic efferents from the ventral subiculum/posteromedial cortical nucleus of the amygdala to other areas of the limbic system modulate the activity of mesolimbic dopaminergic neurons, these findings suggest that oxytocin injected into these areas increases glutamatergic neurotransmission in the ventral tegmental area. This, in turn, activates mesolimbic dopaminergic neurons, leading to penile erection. These results provide evidence that the ventral subiculum and the posteromedial cortical nucleus of the amygdala participate in a neural circuit that controls not only the consummatory aspects of sexual behaviour (e.g. penile erection and copulatory performance), but also its motivational/reward aspects, confirming a key role of oxytocin and dopamine in these processes.

Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats

“…These include the nucleus accumbens (which contains the nerve endings of mesolimbic dopaminergic neurons originating in the ventral tegmental area), the medial preoptic area and the paraventricular nucleus of the hypothalamus (PVN), which are innervated by incerto-hypothalamic dopaminergic neurons of the A13 and A14 groups of Dalsthrom and Fuxe (see [Buijs et al, 1984;Lindvall et al, 1984]). The sexual role of dopamine was confirmed by microinjection studies showing that dopamine agonists and antagonists influence sexual behaviour when injected into the above brain areas [Hull et al, 1986;Melis et al, 1987;Eaton et al, 1989;Chen et al, 1999] and by intracerebral microdialysis studies showing that dopamine concentration is increased in the extracellular dialysate obtained from these brain areas during sexual activity Hull et al, 1995;Pfaus and Everitt, 1994;Melis et al, 1996Argiolas and Melis, 2005;Succu et al 2007;Melis et al, 2007Melis et al, , 2009.…”

Oxytocin enhances the expression of morphine-induced conditioned place preference in rats

“…Indeed, exposure to the previously morphine-paired compartment causes a transient increase in NAc dopamine levels during the expression of morphine-induced CPP (Benturquia et al, 2008). Central oxytocin administration promotes socio-sexual behaviors by enhancing dopamine release in the NAcSh (Melis et al, 2007(Melis et al, , 2009Sanna et al, 2012). Dopamine release within the NAc is dependent on the activity of VTA dopamine neurons (Grace et al, 2007) and oxytocin facilitates responses to social cues via activation of the VTA (Groppe et al, 2013).…”

Mechanisms of Penile Erection and Basis for Pharmacological Treatment of Erectile Dysfunction

“…This may occur also in humans, because plasma oxytocin is increased by sexual stimuli, especially at ejaculation (Carmichael et al, 1987;Murphy et al, 1987). Oxytocin induces penile erection not only when injected into the lateral cerebral ventricle and the PVN but also in other extrahypothalamic brain regions, such as the ventral tegmental area (Melis et al, 2007(Melis et al, , 2009Succu et al, 2008), the ventral subiculum of the hippocampus, and the posterior nucleus of the amygdala (Melis et al, 2009(Melis et al, , 2010, which are important constituents of the limbic system and are thought to play a key role in motivation and reward processes. The erectile response was blocked by oxytocin antagonists and by electrolytic lesion of the PVN.…”