Interaction of neurosteriods-dehydroepiandrosterone sulphate (DHEAS) and androsterone-with cocaine in behavioral despair test (PORSOLT) in rats
Previous studies showed that high plasma levels of endogenous DHEAS correlated with resiliency and ability of cocaine addicts to maintain prolonged abstinence after the therapy (Wilkins et al. 2005), while addicts treated with high dose of exogenous DHEA used more cocaine that those administered placebo (Shoptaw et al. 2004). Such ambiguous outcomes could be due to mixed actions of DHEAS and its metabolite, androsterone, which have opposite neuronal activities. Here we examined acute effects of both neurosteroids in Porsolt test and their interactions with 5 mg/kg of cocaine – the dose reported to have antidepressive action, but which does not infl uence locomotor activity in the open fi eld. Wistar rats (250-300 g) were used. All substances were injected i.p.; steroids 30 min and cocaine 5 minutes before the test, which measures locomotor activity of rats in narrow water containers. Cocaine at dose 5 mg/kg signifi cantly increased rats’ locomotor activity in the Porsolt test. Neither DHEAS (1, 5, 10, 40, 80 mg/kg) nor androsterone (0,1, 1, 10, 40 mg/kg) per se had any effect on activity in this test. DHEAS dose-dependently potentiated the effect of cocaine, but androsterone had no infl uence on this cocaine action. Acutely administered DHEAS appears to increase antidepressive effects of cocaine, but androsterone has no such infl uence. Funded by EC grant MEXC-CT-2006-42371 to M.D. Majewska.
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Warsaw, Poland
- Department of Neurology, Medical University of Warsaw, Warsaw, Poland
- Department of Pharmacology and Physiology of the Central Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland