Effect of HD-23, a potent long acting cocaine-analog, on cocaine self-administration in rats

摘要: "Agonist" therapy for drug addiction proposes that a long acting analog, with similar properties to the abused substance might serve as useful therapeutic agent. HD-23 is very tropane analog displays neurochemical profile cocaine. To determine, using self-administration procedures and three different schedules of reinforcement, effect on rate cocaine intake (fixed ratio), motivation respond (progressive ratio) time course pretreatment (discrete trials). Male Sprague-Dawley rats were implanted chronically indwelling intravenous cannulae trained self-administer (1.5 mg/kg per infusion) fixed ratio schedule. After stable baseline was established, separate groups (n=6–8) given access various doses (0.37, 0.75, 1.5 or 3.0 mg/kg injection) schedule during daily 3-h sessions, (0.18, 0.37, 1.5 mg/kg progressive 5-h sessions. A group (n=10) tested discrete trials procedure; animals opportunity 10-min which initiated every 20 min throughout day/night cycle. On FR schedule, (1.0 mg/kg) decreased intake. shifted dose-response curve PR left. displayed circadian pattern intake; significantly increased about 8 h light phase when probability responding would otherwise have been low. Animals pretreated high 14 h. The results are consistent idea an acute long-acting agonist, HD-23, augmented rather than diminished