TY - JOUR
T1 - DHEA, a neurosteroid, decreases cocaine self-administration and reinstatement of cocaine-seeking behavior in rats
AU - Doron, Ravid
AU - Fridman, Lilach
AU - Gispan-Herman, Iris
AU - Maayan, Rachel
AU - Weizman, Abraham
AU - Yadid, Gal
N1 - Funding Information:
This study was supported in part by a grant from the Israel Science Foundation and from the Israel Anti-Drug Authority to GY. The research reported in this paper was completed as part of the first author’s PhD dissertation, in the Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
PY - 2006/10/7
Y1 - 2006/10/7
N2 - Dehydroepiandrosterone (DHEA), which can act as a potential antidepressant in both animals and humans, appears to lower distress involved with cocaine withdrawal. In fact, a role for neurosteroids in modulation of substance-seeking behavior is becoming increasingly clear. Therefore, we tested the effects of DHEA on the self-administration of cocaine (1 mg/kg/infusion) by rats. At maintenance, a relatively low dose of exogenous DHEA (2 mg/kg; i.p.) attenuated cocaine self-administration after several days of chronic treatment. More than 2 weeks (19 days) of daily DHEA injections were required to decrease the cocaine-seeking behavior of rats to less than 20% of their maintenance levels. DHEA does not seem to decrease cocaine self-administration by increasing the reinforcing properties of the drug, as indicated by a cocaine dose-response determination. After being subjected to extinction conditions in the presence of DHEA, rats demonstrated a minimal response to acute exposure to cocaine (10 mg/kg), which indicated a protective effect of DHEA on relapse to cocaine usage. Our results suggest a potential role for the neurosteroid DHEA in controlling cocaine-seeking behavior, by reducing both the desire for cocaine usage and the incidence of relapse.
AB - Dehydroepiandrosterone (DHEA), which can act as a potential antidepressant in both animals and humans, appears to lower distress involved with cocaine withdrawal. In fact, a role for neurosteroids in modulation of substance-seeking behavior is becoming increasingly clear. Therefore, we tested the effects of DHEA on the self-administration of cocaine (1 mg/kg/infusion) by rats. At maintenance, a relatively low dose of exogenous DHEA (2 mg/kg; i.p.) attenuated cocaine self-administration after several days of chronic treatment. More than 2 weeks (19 days) of daily DHEA injections were required to decrease the cocaine-seeking behavior of rats to less than 20% of their maintenance levels. DHEA does not seem to decrease cocaine self-administration by increasing the reinforcing properties of the drug, as indicated by a cocaine dose-response determination. After being subjected to extinction conditions in the presence of DHEA, rats demonstrated a minimal response to acute exposure to cocaine (10 mg/kg), which indicated a protective effect of DHEA on relapse to cocaine usage. Our results suggest a potential role for the neurosteroid DHEA in controlling cocaine-seeking behavior, by reducing both the desire for cocaine usage and the incidence of relapse.
KW - Cocaine addiction
KW - Dehydroepiandrosterone
KW - Neurosteroid
KW - Reinforcement
KW - Self-administration
KW - Withdrawal
UR - http://www.scopus.com/inward/record.url?scp=33746319313&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1301013
DO - 10.1038/sj.npp.1301013
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C2 - 16421515
AN - SCOPUS:33746319313
SN - 0893-133X
VL - 31
SP - 2231
EP - 2236
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 10
ER -