Chronic oral cocaine self-administration: pharmacokinetics and effects on spontaneous and discriminative motor...

Rats receiving repeated doses of oral cocaine (15 mg/kg) showed replicable increases in large-movement and small-movement activity rates, but sensitization to the repeated doses did not develop. With a schedule-induction procedure, as the daily, 3-hr, oral dose of self-administered cocaine increased, marked dose-related increases occurred in both large-movement locomotor activity rate and the time for which these elevations were sustained during the following daily 2-hr activity session. Sensitization developed. At the highest levels of self-administered oral cocaine (about 80 mg/kg), post-administration serum cocaine levels remained undiminished for the activity-session period, as did the large-movement activities of most animals, indicating no development of acute tolerance. Rats receiving repeated doses of oral cocaine (15 mg/kg) showed discriminative motor control deficits as well as increases in work rate. These changes were dose-related in animals self-administering oral cocaine under the schedule-induction procedure. Upon withdrawal of cocaine from the schedule-induction animals, motor behavior returned to precocaine base-line performance for most animals. The behavior of the animal with the largest cocaine intake did not return. After a schedule-induced oral cocaine intake session, the tail-tip and trunk serum measures for cocaine and its metabolites were approximately equivalent, while brain cocaine and norcocaine levels remained markedly elevated over serum values.