Androsterone has rewarding and aversive prosperities and alters the rewarding effect of cocaine in the conditioned place preference procedure (CPP)
Our previous study showed that the neurosteroid dehydroepiandrosterone sulfate (DHEAS) alters the rewarding effects of cocaine. Because DHEAS is metabolized to androsterone, which has opposite synaptic activity, we wondered about contribution of androsterone to the above phenomenon. Here we examined androsterone’s effect on the rewarding properties of cocaine in CPP test. Male Wistar rats (250–300 g) were used. The CPP procedure consisted of pre-conditioning, conditioning and post-conditioning phases. Drug injections were done i.p. Androsterone alone was rewarding at doses 1 mg/kg and 10 mg/kg, while the dose of 40mg/kg was visibly aversive. Cocaine had a biphasic dose-dependent rewarding effect (inverted U type): the doses 5 and 10 mg/kg were rewarding, while at dose 20 mg/kg, cocaine rewarding effect was lost. Pretreatment with 1mg/kg of androsterone increased the rewarding effect of all cocaine doses, especially the dose of 20 mg/kg, but the rewarding dose of 10 mg/ kg of androsterone had no effect on the rewarding prosperities of cocaine. All doses of cocaine decreased the aversive effect of 40 mg/kg of androsterone. Androsterone per se has a biphasic rewarding-aversive effects in the CPP test and infl uences the rewarding properties of cocaine, which might be explained by two mechanisms: potentiation of reward at low doses and reduction of the aversive effect of the high doses. Funded by EC grant MEXCCT-2006-42371 to M.D. Majewska.
- Department of Neurology, Medical University of Warsaw, Warsaw, Poland
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
- Department of Pharmacology and Physiology of the Central Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland