Withdrawal from continuous or intermittent cocaine: effects of NAN-190 on cocaine-induced locomotion

Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either SC injections or osmotic minipumps. Rats were then withdrawn from the pretreatment regimen for 7 days. In Experiment 1, rats received 0- to 2.0-mg/kg IP injections of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190), a putative 5-hydroxytryptamine1A (5-HT1A) receptor antagonist. In Experiment 2, rats received the same doses of NAN-190 in combination with a 15-mg/kg IP injection of cocaine. The results of Experiment 1 indicate that the continuous-infusion group demonstrated a dose-dependent suppression of locomotor behavior by single doses of NAN-190. NAN-190 had no consistent dose-dependent effect on the locomotor behavior of subjects in the other pretreatment groups. The results of Experiment 2 indicate that rats receiving intermittent, daily injections tended to exhibit behavior consistent with 5-HT1A receptor supersensitivity. In contrast, rats receiving continuous cocaine tended to exhibit behavior consistent with 5-HT1A receptor subsensitivity. Changes in 5-HT1A receptor sensitivity may contribute to some of the anxiety and depressive symptoms exhibited by human cocaine abusers.