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 believ ed to play a role in behavioral sensitization and drug craving experie nced during withdrawal from chronic cocaine administration. The presen t 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 w eeks of TV cocaine self-administration, rats were allowed contingent a ccess to cocaine at 1 and 7 days of withdrawal while extracellular lev els of DA were measured from the ventral striatum. A second group of a nimals 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 fo llowed 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 g roups at either withdrawal time. Extracellular DA levels were increase d throughout the session on both days; however, the increases at day 7 were significantly less than day 1 for both contingent and nonconting ent conditions. DA overflow on day 1 did not differ between animals re ceiving chronic yoked cocaine or saline. These results suggest that to lerance-like attenuation to the DA-elevating effects of cocaine is not apparent early in withdrawal, but does develop by later time points. DA release in the ventral striatum may not be directly related to coca ine self-administration following withdrawal since DA levels were atte nuated after 7 days of withdrawal while responding for cocaine was una ltered.