RT Journal Article
SR Electronic
T1 Repeated Daily Cocaine Alters Subsequent Cocaine-induced Increase of Extracellular Dopamine in the Medial Prefrontal Cortex
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 54
OP 61
VO 281
IS 1
A1 Barbara A. Sorg
A1 Debra L. Davidson
A1 Peter W. Kalivas
A1 Balakrishna M. Prasad
YR 1997
UL http://jpet.aspetjournals.org/content/281/1/54.abstract
AB Male Sprague-Dawley rats that were naive or that had been treated with five daily saline or cocaine injections (15 mg/kg i.p.) were subsequently challenged with an injection of cocaine, and extracellular dopamine content in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis. Cocaine challenge increased extracellular dopamine levels from base line in all three groups of rats, but the augmentation was significantly reduced in the cocaine-pretreated group, compared with the saline-pretreated group. In contrast, mPFC dopamine levels were not different among groups after challenge with systemic d-amphetamine. To test whether repeated cocaine treatment led to altered releasability of dopamine from mPFC terminals, challenge with KCl (10, 30 or 100 mM) ord-amphetamine (3, 30 or 300 μM) was madevia infusion through the dialysis probe into the mPFC. No differences in dopamine levels were found between treatment groups for either drug at any dose. To determine whether the effects of cocaine were mediated by local actions within mPFC dopamine terminals, a cocaine challenge was administered through the microdialysis probe (1, 10 or 100 μM). In contrast to the systemic cocaine challenge, local infusion of cocaine elicited a significant increase in daily cocaine-pretreated rats, compared with saline-pretreated controls, at the lowest dose tested, with no differences at the higher two doses. In summary, daily cocaine-pretreated rats demonstrated a suppressed mPFC dopamine response to subsequent systemic, but not local, cocaine challenge. The results suggest that this apparent tolerance is not due to altered releasability of dopamine from mPFC terminals and may rely on altered afferent regulation of mesocortical dopamine neurons. The American Society for Pharmacology and Experimental Therapeutics