Involvement of dopamine receptors in cocaine-induced genital reflexes after paradoxical sleep deprivation.
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 [3H] 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 D2 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 D1 and D2 receptors may play a role in these effects.
Andersen
Monica Levy
ML
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. mandersen@sti.com.br
Papale
Ligia Assumpção
LA
Hipólide
Débora Cristina
DC
Nobrega
José N
JN
Tufik
Sergio
S
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D011954:Receptors, Dopamine / Q000378:metabolism*; D012892:Sleep Deprivation / Q000503:physiopathology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D014316:Tritium / Q000494:pharmacology
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D011954:Receptors, Dopamine; D014316:Tritium; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D003042:Cocaine