Dehydroepiandrosterone sulphate (DHEAS) is rewarding and alters the rewarding effect of cocaine in the conditioned place preference procedure (CPP)
DHEAS is endogenous allosteric antagonists of the GABA(A) receptor and has other direct and indirect actions in CNS. It is metabolized to other neuroactive steroids. Prior studies revealed an ambiguous role of DHEA(S) in cocaine dependence, suggesting interactions with cocaine effects in the brain. This preclinical study was undertaken to evaluate direct infl uence of DHEAS on the rewarding effects of cocaine, using the CPP test in rats. Male Wistar rats (250–300 g) were used. The conditioned place preference experiment consisted of preconditioning conditioning and post-conditioning phases. Drug injections were done i.p. only during the conditioning phase. Cocaine had a biphasic dose-dependent rewarding effect (inverted U type). The doses 5 and 10 mg/kg were clearly rewarding, as they increased rats’ preference for cocaine injection site, while at the dose 20 mg/kg, cocaine rewarding effect was lost. DHEAS alone had a similar biphasic rewarding effect (the effect of 40 mg/kg was maximal and statistically signifi cant). Pretreatment of rats with 40 mg/kg of DHEAS before injection of cocaine noticeably changed its rewarding effect, shifting cocaine dose response curve to the left. DHEAS, per se has rewarding properties and it enhances the rewarding effects of low doses of cocaine, but decreases the rewarding effect of higher doses of cocaine. Funded by EC grant MEXC-CT-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