Withdrawal of repeated intravenous infusions of cocaine persistently reduces binding to dopamine transporters in the nucleus accumbens of Lewis rats.

Male, Lewis rats were administered cocaine or saline i.v. in an intermittent fashion for 5, 10 or 20 days and killed at various times afterwards. Dopamine transporter binding was then measured in dorsal striatum and nucleus accumbens. Transporter binding was not changed in dorsal striatum under any conditions tested. In the nucleus accumbens, however, binding was decreased in animals given cocaine (10 mg/kg total) for 10 days and withdrawn for 10, 30 or 60 days, but not in animals withdrawn for 0, 1, 3 and 6 days. There were no changes in animals given cocaine for 5 days and withdrawn for 10, or in animals given drug for 20 days and withdrawn for 1 day. Animals given only 1/10 of the cocaine dose had no changes in nucleus accumbens after 10 days of administration and 10 days of withdrawal. Scatchard analysis in control animals indicated that there were significant differences in both Kd and Bmax when comparing nucleus accumbens with dorsal striatum. Within the nucleus accumbens, decreases in binding after a cessation of cocaine administration were associated with a change in Bmax and not in Kd. These data indicate that long-lasting changes in the mesolimbic dopaminergic system can occur during the withdrawal period, and may contribute to behavioral effects during this period.