Continuous or intermittent cocaine administration: Effects of amantadine treatment during withdrawal

Research indicates that daily cocaine injections produce sensitization to, while the continuous infusion of cocaine produces tolerance to, its behavioral and neurochemical effects. The effects of the continuous infusion of cocaine are consistent with the withdrawal syndrome reported by human cocaine abusers. The present experiment examined whether amantadine administrations during withdrawal from continuous or intermittent cocaine attenuate and/or eliminate the behavioral effects produced by these administration regimens. The rats were pretreated for 14 days with either continuous or intermittent daily injections of cocaine, and were then withdrawn from the pretreatment regimen for 7 days. On days 1–5 of the withdrawal period, half the subjects received a 5.0 mg/kg IP injection of amantadine, and the other half received a 20.0 mg/kg IP injection of amantadine. On day 7 of withdrawal from the cocaine pretreatment, all rats were given a 15.0 mg/kg IP injection of cocaine. Their behavior was rated according to the modified Ellinwood and Balster (6) scale for 60 min. The results indicated that amantadine treatment during withdrawal eliminated the tolerance normally associated with the continuous infusion of cocaine. In contrast, in both the saline control and daily injection subjects amantadine treatment during withdrawal resulted in a slight, but statistically significant, reduction in the behavioral effects of cocaine. The present results therefore indicate that low doses of amantadine should be considered as a potential pharmacotherapy for the early stages of cocaine withdrawal. Furthermore, the present experimental procedures may represent an effective screening methodology for potential cocaine pharmacotherapies.