Involvement of nitric oxide in cocaine-induced erections and ejaculations after paradoxical sleep deprivation Monica L. Andersen ⁎ , Juliana C. Perry, Isabela B. Antunes, Sergio Tufik Department of Psychobiology — Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), R. Napoleão de Barros, 925, V. Clementino 04024-002, São Paulo, SP, Brazil Received 20 September 2006; received in revised form 14 December 2006; accepted 16 December 2006 Available online 28 December 2006 Abstract Objectives: As nitric oxide (NO) is involved in penile erectile (PE) function and also influences the sleep–wake cycle, we speculated that NO could play a role in PE and ejaculation of paradonical sleep deprivation (PSD) rats. Methods: Animals were pretreated with N G -nitro-L-arginine methyl ester (L-NAME, ip) and L-arginine (ip and icv) prior to saline or cocaine injection. Results: Cocaine-induced PE in 90% of PSD rats, 60% of which ejaculated. L-NAME reduced the frequency of erection, but had no effect in the proportion of PSD-cocaine-injected rats displaying this response. L-NAME had no effect in saline groups. L-Arginine in PSD-saline rats reduced the proportion of animals displaying PE at the highest dose and reduced the frequency of PE at all doses in both saline and cocaine groups. The icv administration of L-arginine reduced PE only in PSD-cocaine rats. Results indicate that common to both drugs, whether it was NO synthase (NOS) inhibitor or NO precursor, was their capacity to strongly reduce PE frequency in cocaine-treated rats. Moreover, L-arginine (ip) played a relevant inhibitory role in the erection displayed by PSD rats. Conclusions: Our findings suggest that the stimulating effects of PSD associated or not with cocaine on erection can be modified by alterations in the NO system. © 2006 Elsevier Inc. All rights reserved. Keywords: Cocaine; Erection; L-Arginine; L-NAME; Nitric oxide; Rat; Sleep deprivation 1. Introduction It has already been demonstrated that nitric oxide (NO) plays a crucial role in the control of erectile function (Burnett, 2005). Sexual stimulation leads to NO production that in turn stimulates guanylate cyclase that converts guanosine triphos- phate to cGMP resulting in relaxation of the smooth muscles of penile arteries and corpus cavernosum (Burnett, 1997, 2005). The implication of NO in sexual behavior is derived from the fact that systemic administration of NO synthase (NOS) inhibitor N G -nitro-L-arginine methyl ester (L-NAME) impaired copulation (Hull et al., 1994, 1997). This probably was due to an inhibition of erectile ability. Drug-treated males were unable to achieve vaginal intromissions during most mounts, and had fewer penile erections (Moses and Hull, 1999) suggesting that NO promotes erection in intact males probably by mediating the filling of the corpora cavernosa of the penis (Rajfer et al., 1992). Besides peripheral mechanisms, central effects of NO af- fecting erection in male rats have not been completely ruled out (Bialy et al., 1996). NO may influence these behaviors through release of a variety of neurotransmitters, among them, dopamine (DA) (Lorrain and Hull, 1993). In fact, NO promotes DA release in the medial preoptic area (MPOA) (Lorrain et al., 1996; Hull et al., 1997). In rats, injection of NOS inhibitors intracerebroven- tricularly or in the paraventricular nucleus (PVN) prevented penile erection (PE) responses induced by dopaminergic agonists (Melis and Argiolas, 1993). Finally, the L-NAME inhibitory effects on sexual behavior have been attributed to a decrease of blood flow within the penis, an increase in the adrenergic drive to Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 652 – 657 www.elsevier.com/locate/pnpbp ⁎ Corresponding author. Department of Psychobiology— Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, Vila Clementino— SP- 04024-002, São Paulo, Brazil. Tel.: +55 11 2149 0155; fax: +55 11 5572 5092. E-mail address: mandersen@psicobio.epm.br (M.L. Andersen). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.12.012