Tolerance-like attenuation to contingent and noncontingent cocaine-induced elevation of extracellular dopamine in the ventral striatum following 7 days of withdrawal from chronic treatment.
Time-dependent changes in mesolimbic dopamine (DA) function are believed to play a role in behavioral sensitization and drug craving experienced during withdrawal from chronic cocaine administration. The present study utilized intravenous (IV) cocaine self-administration coupled with intracranial microdialysis in rats to investigate time dependent changes during withdrawal from chronic cocaine exposure. Following 2 weeks of IV cocaine self-administration, rats were allowed contingent access to cocaine at 1 and 7 days of withdrawal while extracellular levels of DA were measured from the ventral striatum. A second group of animals received yoked, noncontingent cocaine for 2 weeks and were then administered noncontingent cocaine on days 1 and 7 of withdrawal. In addition, a third group of animals received 2 weeks of yoked saline followed by noncontingent cocaine 1 day after withdrawal. There were no significant differences between groups for the overall cocaine dosage or temporal pattern of infusions on days 1 and 7 of withdrawal. Basal extracellular DA concentrations did not differ between any treatment groups at either withdrawal time. Extracellular DA levels were increased throughout the session on both days; however, the increases at day 7 were significantly less than day 1 for both contingent and noncontingent conditions. DA overflow on day 1 did not differ between animals receiving chronic yoked cocaine or saline. These results suggest that tolerance-like attenuation to the DA-elevating effects of cocaine is not apparent early in withdrawal, but does develop by later time points.(ABSTRACT TRUNCATED AT 250 WORDS)
Meil
W M
WM
Department of Psychology, Washington State University, Pullman 99164-4820, USA.
Roll
J M
JM
Grimm
J W
JW
Lynch
A M
AM
See
R E
RE
D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004361:Drug Tolerance; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D013997:Time Factors
D003042:Cocaine; D004298:Dopamine