Oxytocin induces penile erection and yawning when injected into the bed nucleus of the stria terminalis: A microdialysis and immunohistochemical study

Oxytocin, Erectile Function and Sexual Behavior: Last Discoveries and Possible Advances

“…By acting as an intra- or intercellular messenger, NO activates glutamic acid neurotransmission. This induces penile erection, possibly through the activation of glutamatergic efferent projections from the ventral subiculum to the extra-hippocampal brain areas that modulate the activity of mesolimbic dopaminergic neurons (i.e., the ventral tegmental area, the prefrontal cortex, the PVN, and possibly the bed nucleus of the stria terminalis) ( Figure 4 , see below and [ 23 , 24 , 88 , 89 , 168 , 180 , 181 ]). Accordingly, intracerebral microdialysis experiments show that in male rats, oxytocin injected into the ventral subiculum at doses that induce penile erection increases NO production and extra-cellular glutamic acid in the dialysate obtained from the ventral subiculum [ 180 ] and of extra-cellular dopamine in the nucleus accumbens and medial prefrontal cortex [ 180 , 181 ].…”

“…The PVN and surrounding periventricular structures also contain the cell bodies of parvocellular oxytocinergic neurons that project to extra-hypothalamic brain areas (i.e., medial preoptic area, ventral tegmental area, hippocampus, amygdala, septum, bed nucleus of the stria terminalis, medulla oblongata, and spinal cord) (see [ 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]). Since their discovery in the 1980s (see [ 14 , 15 ]), these central oxytocinergic neurons have been involved in numerous central functions, i.e., memory; learning; affiliative and socio-sexual behaviors, from erectile function to copulatory behavior; yawning, and many others, from the control of pain and feeding behavior to drug dependence (see [ 3 , 4 , 5 , 6 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]). In the last fifteen years, there have been many reports that have appeared and that are still appearing that have reported the effects of intranasal oxytocin, a delivery route believed to allow the crossing of the blood–brain barrier by the peptide, which can then reach and act at the level of the central nervous system (see [ 25 ]).…”

Altered Sexual Behavior in Dopamine Transporter (DAT) Knockout Male Rats: A Behavioral, Neurochemical and Intracerebral Microdialysis Study

“…Indeed, although both dopamine and glutamic acid concentrations increased above basal values in WT more than in DAT KO rats during sexual activity, with dopamine concentration increased during the entire period of sexual activity in all the three rat lines, glutamic acid increased in DAT KO rats only in the last period of sexual activity, at variance from WT and HET rats, in which it increased significantly already in the first period of sexual activity. It is reasonable to assume that these differential changes in dopamine and glutamic acid outputs are involved in the differences in sexual behavior among the three rat lines, since dopamine and glutamic acid, together with the neuropeptide oxytocin, are key neurotransmitters of a complex brain circuit that interconnects hypothalamic, limbic and cortical areas involved in both the motivational and performance aspects of the male rat sexual behavior (Melis and Argiolas, 2011;Argiolas and Melis, 2013;Sanna et al, 2017a;Bratzu et al, 2019;Melis et al, 2019). Finally, differences were also detected among DAT KO, HET and WT rats in the expression of BDNF and its trkB receptor, markers of neural activation (∆-FosB) and plasticity (Arc and PSA-NCAM) and synaptic structural proteins (synaptophysin, syntaxin-3, PSD-95) in the VTA, mPFC, and Acb (shell and core), which are all brain areas relevant for sexual motivation and sexual performance.…”

“…The glutamic acid concentration in the dialysate from the Acb shell was measured in the same dialysate aliquots used for the measurement of dopamine as previously described (Succu et al, 2011;Bratzu et al, 2019). Briefly, glutamic acid concentration was measured in 5 µl aliquots of dialysate added to 5 µl of HClO 4 100 mM after pre-column derivatization with orto-phtalaldialdehyde and 2-mercaptoethanol by HPLC.…”

“…Nevertheless, it is reasonable to assume that some, if not all, of the above differences in sexual behavior among DAT KO, HET and WT rats may be mediated, at least in part, by an altered interaction between Acb dopamine and glutamic acid. Infact, it is well accepted that: (i) the function of mesolimbic and mesocortical dopaminergic neurons, which play a key role in motivated behavior (Goto and Grace, 2005) and have their cell bodies mainly in the VTA, is finely modulated by the activity of glutamic acid neurons, which originate, although not exclusively, from the PFC and project to the Acb and to the VTA (Carlsson et al, 2001;Carlezon and Thomas, 2009;Beloate and Coolen, 2017;Bamford et al, 2018); (ii) an intact glutamatergic function in the PFC is required for cortical control over the activity of the dopaminergic mesolimbic system to modulate, together with dopamine release, the activity of the GABAergic medium spiny neurons at the level of the Acb and motivated behavior (Carlsson et al, 2001;Kalivas, 2009); and (iii) dopamine and glutamic acid, together with the neuropeptide oxytocin, are key neurotransmitters in the functioning of a complex brain circuit, interconnecting hypothalamic, limbic and cortical areas, involved in both the motivational and performance aspects of male rat sexual behavior (Melis et al, 2007(Melis et al, , 2009(Melis et al, , 2010Succu et al, 2007Succu et al, , 2008Succu et al, , 2011Melis and Argiolas, 2011;Sanna et al, 2017a;Bratzu et al, 2019).…”