title: Dehydroepiandrosterone Attenuates Cocaine-Seeking Behaviour Independently of Corticosterone Fluctuations.
abstract: The neurosteroid dehydroepiandrosterone (DHEA) is involved in the pathophysiology of several psychiatric disorders, including cocaine addiction. We have previously shown that DHEA attenuates cocaine-seeking behaviour, and also that DHEA decreases corticosterone (CORT) levels in plasma and the prefrontal cortex. Previous studies have found that rats demonstrate cocaine-seeking behaviour only when the level of CORT reaches a minimum threshold. In the present study, we investigated whether the attenuating effect of DHEA on cocaine seeking is a result of it reducing CORT levels rather than a result of any unique neurosteroid properties. Rats received either daily DHEA injections (2 mg/kg, i.p.) alone, daily DHEA (2 mg/kg, i.p.) with CORT infusion (to maintain stable basal levels of CORT; 15 mg/kg, s.c.) or vehicle (i.p.) as control, throughout self-administration training and extinction sessions. We found that both DHEA-treated and DHEA + CORT-treated groups showed a significantly lower number of active lever presses compared to controls throughout training and extinction sessions, as well as at cocaine-primed reinstatement. DHEA-treated rats showed lower CORT levels throughout the experimental phases compared to DHEA + CORT-treated and control rats. Additionally, we show that DHEA administered to cocaine-trained rats throughout extinction sessions, or immediately before reinstatement, attenuated cocaine seeking. These findings indicate that DHEA attenuates cocaine-seeking behaviour independently of fluctuations in CORT levels.
authors: The Laboratory of Biological Psychiatry, Felsenstein Medical Research Center and Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.
authors: R
authors: R
authors: Maayan
authors: Leslie and Gonda (Goldschmied) Multidisciplinary Brain Research Center, Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: L
authors: L
authors: Hirsh
authors: Leslie and Gonda (Goldschmied) Multidisciplinary Brain Research Center, Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors: G
authors: G
authors: Yadid
authors: The Laboratory of Biological Psychiatry, Felsenstein Medical Research Center and Sackler Faculty of Medicine, Tel Aviv University, Petah Tikva, Israel.|Geha Mental Health Center, Petah Tikva, Israel.
authors: A
authors: A
authors: Weizman
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D007260:Infusion Pumps; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D012646:Self Administration
chemical_list: D003687:Dehydroepiandrosterone; D003042:Cocaine; D003345:Corticosterone
keywords: cocaine self-administration; corticosterone; dehydroepiandrosterone