The present results show an increase in locomotor activity 24 h following repeated cocaine administration only with the higher dose (10 mg/kg, IP, daily for 1 week) compared to controls (administered with saline). Binding assays were done and the ligands used were [ 3 H]N-methylscopolamine ([ 3 H]-NMS), [ 3 H]-SCH 23390, and [ 3 H]-spiroperidol to determine muscarinic (M 1 - and M 2 -like), D 1 and D 2 receptors, respectively. Scatchard analyses revealed alterations in B m a x not only for muscarinic, but also for D 2 -like receptors that were significantly increased. On the other hand, no alterations were detected on D 1 -like receptors densities and dissociation constant values. However, the K d value was significantly increased for D 2 receptors. The changes in muscarinic receptors were observed predominantly on M 2 -like, which presented an increase of 84% with the 10 mg/kg, IP, dose only. On D 2 -like receptors, increases of 63 and 54% were demonstrated with the doses of 5 and 10 mg/kg, IP. The preferential effects of cocaine on muscarinic and D 2 -like receptors were also demonstrated in vitro where decreases in [ 3 H]-NMS and [ 3 H]-spiroperidol binding were observed. The results indicate that the effects of cocaine on muscarinic and dopaminergic postsynaptic receptors are functions of dose, duration of treatment, and time of drug withdrawal.