Sensitization to cocaine and dopamine autoreceptor subsensitivity in the nucleus accumbens.
It has been suggested that dopamine autoreceptor subsensitivity may play a role in cocaine-induced behavioral sensitization. In order to evaluate this hypothesis, we administered cocaine to rats daily (15 mg/kg ip x 2 days, 30 mg/kg ip x 5 days) and then monitored nucleus accumbens dopamine during the local administration (through the dialysis probe) of the D2/D3 agonist, quinpirole (0, 0.1, 1, and 10 microM). Our results indicate that, relative to saline-pretreated control animals, repeated cocaine administration impaired the ability of quinpirole to decrease extracellular dopamine 1-2 days after the last drug injection. However, quinpirole was equipotent at reducing accumbal dopamine in cocaine- and saline-treated animals following a 21-22 day withdrawal period. These results demonstrate that repeated cocaine produces a short duration functional tolerance in the capacity of autoreceptor stimulation to inhibit accumbal dopamine release.
Pierce
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Alcoholism and Drug Abuse Program, Washington State University, Pullman 99164-6530, USA.
Duffy
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Kalivas
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D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000187:drug effects*; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D003042:Cocaine; D004298:Dopamine