Oxytocin induces penile erection when injected into the ventral subiculum: Role of nitric oxide and glutamic acid

Oxytocin (100 ng) induces penile erection when injected unilaterally into the ventral subiculum of the hippocampus of male rats. The pro-erectile effect started mostly 30 min after treatment and occurred 15 min after an increase in both nitric oxide (NO) production, measured by the concentration of NO2− and NO3−, the main metabolites of newly formed NO, and extra-cellular glutamic acid concentration in the dialysate obtained from the ventral subiculum by intracerebral microdialysis. These responses were abolished by d(CH2)5Tyr(Me)2-Orn8-vasotocin (2 μg), an oxytocin receptor antagonist, S-methyl-l-thiocitrulline (SMTC), a selective inhibitor of neuronal NO-synthase (25 μg), and haemoglobin, a NO scavenger (25 μg), given into the ventral subiculum before oxytocin. Unlike d(CH2)5Tyr(Me)2-Orn8-vasotocin, SMTC and haemoglobin, (+)MK-801 (5 μg), a noncompetitive antagonist of NMDA receptors abolished oxytocin-induced penile erection, but reduced only partially the increase in NO production and extra-cellular glutamic acid. As NMDA (0.25–1 μg) injected into the ventral subiculum induces penile erection episodes, which also occurred with an increase of NO production and extra-cellular glutamic acid, and NMDA responses were abolished by (+)MK-801 (5 μg), but not by SMTC (25 μg) or haemoglobin (25 μg), injected into the ventral subiculum, these results show that oxytocin injected into the ventral subiculum increases NO production by activating its own receptors. NO in turn increases glutamic acid neurotransmission, leading to penile erection, possibly through neural (glutamatergic) efferent projections from the ventral subiculum to extra-hippocampal brain areas (e.g., prefrontal cortex) modulating the activity of mesolimbic dopaminergic neurons.