La somministrazione di ossitocina nel nucleo del letto della stria terminale del ratto induce erezione peniena e sbadiglio: studi comportamentali, neurofarmacologici e neurochimici sul meccanismo d’azione.

The bed nucleus of the stria terminalis (BNST) is a complex forebrain structure that plays an key role in autonomic, neuroendocrine and behavioral responses such as anxiety, fear, stress and sexual behavior. The control of these functions by the BNST is mediated by neurotransmitters as GABA, glutamic acid, dopamine, serotonin, nitric oxide (NO), and neuropeptides as corticotrophin releasing factor (CRF) and oxytocin. Interestingly, i) oxytocin and oxytocin receptors are present in the BNST, ii) all oxytocin neurons present in the central nervous system originate from the paraventricular nucleus of the hypothalamus, and iii) some of these neurons control penile erection, sexual behavior and yawning. This raises the possibility that oxytocin may also play a role in the control of these responses at the level of the BNST. To test this possibility, the effect of oxytocin injected into the BNST on these responses was studied. Oxytocin (5-100ng), but not Arg8-vasopressin (100ng), injected unilaterally into the BNST induced penile erection and yawning in a dose-dependent manner in male rats. The minimal effective dose was 20ng for penile erection and 5ng for yawning. Oxytocin responses were abolished by the oxytocin receptor antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (1μg), (+) MK-801 (1μg), an excitatory amino acid receptor antagonist of the N-methyl-d-aspartic acid (NMDA) subtype, SCH 23390 (1μg), a D1 receptor antagonist, but not haloperidol (1μg), a D2 receptor antagonist, and SMTC (40μg), an inhibitor of neuronal nitric oxide synthase, injected into the BNST 15min before oxytocin. Oxytocin-induced penile erection, but not yawning, was also abolished by CNQX (1μg), an excitatory amino acid receptor antagonist of the AMPA subtype. In contrast, oxytocin responses were not reduced by bicuculline (20ng), a GABAA receptor antagonist, phaclofen (5μg), a GABAB receptor antagonist, CP 376395, a CRF receptor-1 antagonist (5μg), or astressin 2B, a CRF receptor-2 antagonist (150ng). Since NMDA (100 ng) also induced penile erection and yawning when injected into the BNST, but NMDA responses were not antagonized by pretreatment with d(CH2)5Tyr(Me)2-Orn8-vasotocin, these results suggest that oxytocin induces penile erection and yawning by activating glutamatergic neurotransmission in the BNST. This in turn leads to the activation of neural pathways projecting back to the paraventricular nucleus, medial preoptic area, ventral tegmental area, and/or ventral subiculum/amygdala, thereby inducing penile erection and yawning. In line with this mechanism of action, intracerebral microdialysis experiments showed that i) oxytocin (100 ng) injected into the BNST not only induces penile erection and yawning, but also increases the concentrations of extracellular glutamic acid and NO2- ions (a measure of NO production) in the dialysate obtained from the BNST, and ii) both effects are abolished by pre-treatment with d(CH2)5Tyr(Me)2-Orn8-vasotocin (1μg) given into the BNST before oxytocin