Behavioural Brain Research 160 (2005) 44–50 Research report Involvement of dopamine receptors in cocaine-induced genital reflexes after paradoxical sleep deprivation Monica Levy Andersen a,∗ , Ligia Assumpc ¸˜ ao Papale a , D´ ebora Cristina Hip ´ olide a , Jos´ e N. Nobrega b , Sergio Tufik a a Department of Psychobiology, Universidade Federal de S˜ ao Paulo, Escola Paulista de Medicina (UNIFESP/EPM), R. Napole ˜ ao de Barros, 925, V. Clementino 04024-002, S˜ ao Paulo, SP, Brazil b Neuroimaging Research Section, Centre for Addiciton and Mental Health, 250 College St., Toronto, Ont., Canada M5T 1R8 Received 5 July 2004; received in revised form 17 September 2004; accepted 14 November 2004 Available online 28 December 2004 Abstract Previous work has demonstrated that paradoxical sleep deprivation (PSD) potentiates cocaine-induced genital reflexes in male rats. To examine the possibility that this effect might involve alterations in binding to the DA transporter (DAT), we examined [ 3 H] WIN 35,248 binding in brain after 96 h of PSD. No changes were found in any of the 11 brain regions examined. Since we had previously identified changes in D 2 receptor binding after PSD, we next examined the effects of DA receptor subtype antagonists on cocaine-induced reflexes in sleep-deprived rats. Separate groups of PSD rats received saline, haloperidol (0.4, 0.8 or 1.6 mg/kg), SCH 23390 (0.25, 0.5, 1 mg/kg) or sulpiride (50, 100, 200 mg/kg) 60 min prior to acute cocaine (7 mg/kg). In saline pretreated rats, cocaine-induced penile erection (PE) in 100% of SD rats. This percentage was not significantly reduced by haloperidol at any dose, but was significantly reduced in rats pretreated with SCH 23390 (1 mg/kg) or sulpiride (100 or 200 mg/kg). In addition, acute cocaine-induced ejaculation in 80% of SD rats. This effect was not affected by haloperidol at any dose, but was significantly reduced by all doses of SCH 23390 and by the 200 mg/kg dose of sulpiride. These results suggest that the potentiating effects of cocaine on penile erection and ejaculation are likely due to PSD-induced changes in DA postsynaptic receptor sensitivity rather than alterations in DA transporter. They further suggest that both D 1 and D 2 receptors may play a role in these effects. © 2004 Elsevier B.V. All rights reserved. Keywords: Sleep deprivation; DAT; Haloperidol; SCH 23390; Sulpiride; WIN 35,248; Erection; Ejaculation; Cocaine 1. Introduction Dopamine (DA) has received a substantial amount of at- tention with respect to its effect on sexual behavior in both rats and humans. It is well known that administration of drugs that enhance brain DA neurotransmission results in facilita- tion of male rat sexual behavior [12,27,29,33] and alleviates impotence in men [35]. Conversely, DA antagonists reduce male rat sexual behavior [18,33]. Psychomotor drugs of abuse that stimulate DA release and/or block DA uptake, such as amphetamine and cocaine, ∗ Corresponding author. Tel.: +55 11 5539 0155; fax: +55 11 5572 5092. E-mail address: mandersen@sti.com.br (M.L. Andersen). are considered “prosexual” [1]. In fact, cocaine is rated as the most effective drug for increasing libido and sexual per- formance [2,23]. Cocaine’s effects on sexual excitement are likely due to stimulation of mesolimbic DA reward/pleasure pathways [13,24,37]. The stimulating effects of cocaine and amphetamine are in large measure due to their ability to block the DA transporter (DAT), thereby increasing synaptic DA levels [41]. Paradoxical sleep deprivation (PSD) has been known for some time to potentiate a number of behavioral responses, in particular aggressive and stereotyped behaviors in re- sponse to dopamine agonists [38,39]. More recently, sexual responses to dopaminergic agonists have also been shown to be potentiated after PDS [4–7,20]. Thus our previous 0166-4328/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2004.11.016