Oxytocin induces penile erection and yawning when injected into the bed nucleus of the stria terminalis: involvement of glutamic acid, dopamine and nitric oxide

OXYTOCIN INDUCES PENILE ERECTION AND YAWNING WHEN INJECTED INTO THE BED NUCLEUS OF THE STRIA TERMINALIS: INVOLVEMENT OF GLUTAMIC ACID, DOPAMINE AND NITRIC OXIDE. The bed nucleus of the stria terminalis (BNST) is a complex forebrain structure divided in different subregions, which plays an important role in autonomic, neuroendocrine and behavioral responses such as anxiety, fear, stress and sexual behavior. The control of physiological and behavioral activities exerted by the BNST is mediated through the action of various neurotransmitters including GABA, glutamic acid, dopamine, serotonin, nitric oxide (NO), and neuropeptides as corticotrophin releasing factor (CRF) and oxytocin [1]. The presence of oxytocin and oxytocin receptors in the BNST together with the fact that all oxytocin neurons present in the central nervous system originate from the paraventricular nucleus of the hypothalamus and that some of these neurons exert a facilitatory role on penile erection and sexual behavior and on yawning as well [2,3], raise the possibility that oxytocin may play a role in the control of penile erection, sexual behavior and yawning at the level of this brain area. In order to verify such possibility, we studied the effect of the injection of oxytocin into the BNST on penile erection and yawning and its possible interaction with other BNST neurotransmitter systems in inducing these effects. Briefly, male Sprague Dawley rats were stereotaxically implanted unilaterally with a stainless-steel guide cannula (22 gauge) aimed at the BNST under isoflurane anaesthesia. After surgery, rats were given 7 days for recovery. Microinjections of oxytocin and other compounds usually dissolved in saline or appropriate vehicles were performed through an internal cannula (28 gauge) extending 6 mm below tip of the guide cannula (Paxinos & Watson, The stereotaxic atlas of the rat brain, 2004) in a volume of 0.3 µL in 2 min. Rats injected with saline or vehicle alone were used as controls. Oxytocin (5-100 ng) but not vasopressin (100 ng) injected into the BNST, dose-dependently induced penile erection and yawning. The minimal effective dose of oxytocin was 20 ng for penile erection and 5 ng for yawning, while the maximum effect was found for both responses with the dose of 100 ng. Oxytocin responses were completely abolished by the oxytocin receptor antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (1 µg) injected into the BNST 15 min before oxytocin. Penile erection and yawning were also abolished by the prior injection into the BNST of (+) MK-801 (1 µg) and CNQX (1 µg), excitatory amino acid receptor antagonists, the first of the NMDA and the second of the AMPA receptor subtype, respectively, by SCH 23390 (1 µg), a D1 receptor antagonist and by SMTC (40 µg), an inhibitor of neuronal nitric oxide synthase. In contrast, no effect on oxytocin-induced penile erection and yawning was found when haloperidol, a D2 receptor antagonist, (1 µg), bicuculline (20 ng) and phaclophen (5 µg), a GABAA and GABAB receptor antagonist, respectively, and CP 376395 (5 µg) and astressin 2B (150 ng), CRF receptor antagonists, the first of the CRF-1 and the second of the CRF-2 receptor subtype, were given into the BNST 15 min prior oxytocin. Finally, the excitatory amino acid N-methy-D-aspartic acid (NMDA) (100 ng) per sé was able to induce penile erection and yawning when injected into the BNST, and these effects were antagonized by the prior injection of (+) MK-801 (1 µg) into the BNST. Taken together, the results of this study show that oxytocin injected into the BNST induces penile erection and yawning in a dose dependent manner and that this effect can be attributed to the interaction of BNST oxytocin neurons with BNST dopaminergic, glutamatergic and nitric oxide pathways and not through CRF and/or GABAergic pathways. The involvement of glutamic acid and NMDA receptors in the pro-erectile and proyawning effects of oxytocin at the level of the BNST is also supported by the ability of NMDA given into the BNST to induce both penile erection and yawning.