Sensitization of operant behavior to oral cocaine with increasing- and repetitive-dose regimens

This study evaluated whether operant behavior was subject to sensitization upon repeated exposure to cocaine. The behavior of eight rats was reinforced by food-pellet delivery under a differential reinforcement of low-rate (DRL) 45-s schedule, in daily sessions of 190 min. Each session was composed of five 35-min subsessions, with each subsession preceded by a 3-min time out period (TO). For selected sessions, a cumulative dose-effect relation for cocaine, using increasing doses, was first determined by oral gavage administration of a dose during each subsession. Three such cycles were given, separated by between seven and ten sessions. Later, four further cycles were given, using a repetitive 10 mg/kg cocaine per os (p.o.) dose, rather than an increasing dose. Under both dosing procedures, within a cocaine cycle (session), shorter (<45 s) inter-response times (IRT) progressively increased with doses, and reinforced responses decreased. As cycles were repeated, the shorter IRT increases became progressively more marked, indicating the development of sensitization to the effect of cocaine. With the second procedure (repetitive 10 mg/kg doses), reinforcement rate decreases became more marked as cycles were repeated, but this change did not occur using the increasing-dose procedure. Upon later exposure to repetitive 5 mg/kg dosing cycles, none of these rate changes occurred, and performances were equivalent to those occurring under saline cycles. Exposure to cumulative dose regimens of oral cocaine can result in the sensitization of operant behavior to the effects of cocaine.