Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration.
The effects of withdrawal from cocaine on extracellular dopamine (DA) levels in the nucleus accumbens (NAC) were examined by intracranial microdialysis in awake rats after periods (9.5-21.75 h) of unlimited-access, intravenous cocaine self-administration. Cocaine withdrawal was associated with significant reductions in basal DA overflow that persisted up to 12 h. Maximal inhibition of DA release (mean +/- S.E.M. 66.15 +/- 3.30 percent of basal levels) was observed between 4-6 h after cessation of cocaine intake and was positively correlated (r = 0.88) with the duration of the preceding self-administration episode. The results suggest that suppression of basal DA release in the NAC is an adaptive consequence of sustained cocaine exposure and may in part underlie the post-cocaine anhedonia observed in behavioral models of cocaine withdrawal.
Weiss
F
F
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Markou
A
A
Lorang
M T
MT
Koob
G F
GF
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012646:Self Administration; D013238:Stereotaxic Techniques; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors
D003042:Cocaine; D004298:Dopamine