Behavioral mechanisms underlying the extinction of cocaine self-administration

Abstract

The aim of the present series of experiments was to outline the influence of different doses of cocaine during training, training schedule, training length and abstinence duration to modulate subsequent extinction and reinstatement patterns. Abram Amsel’s general theory of persistence were used to both design and explain various aspects of these models. For Experiment 1, rats self-administered cocaine (0.25, 0.50 or 1.00 mg/kg) intravenously and were then tested in an extinction preparation using saline infusions (5 days) and then only the stimulus light as the reinforcer (3 days). Experiment 2 examined schedules by magnitude interactions by training rats on two fixed-ratio (FR) schedules (FR-1 or FR-10 using either 0.25 or 1.00 mg/kg cocaine). Animals were tested in an extinction protocol (10 days; no stimulus light) and subsequently tested for reinstatement (1 day) that utilized presentations of the stimulus light. Experiment 3 addressed the effects of training length (15 or 30 days of training using either 0.25 or 1.00 mg/kg cocaine) using the same protocol as in Experiment 2. Experiment 4 examined the modulation potential of two abstinence lengths (15 or 30 days using either 0.25 or 0.50 mg/kg cocaine) using the same conditions as Experiment 2. Experiment 1 indicated the greatest resistance to extinction using the lowest training dose (0.25 mg/kg). The removal of saline caused an apparent extinction burst indicative of reward seeking. Experiment 2 showed that animals trained under partial reinforcement schedules persisted more during extinction. Furthermore, rats trained using 1.00 were more resistant than those trained with 0.25 mg/kg. Reinstatement of drug seeking was more pronounced in rats trained using an FR-10 schedule. Experiment 3 indicated greater resistance to extinction in rats trained for 15 versus 30 days. Rats trained on 0.50 mg/kg for 30 days showed less cue-induced reinstatement than those trained for 15 days. Experiment 4 showed increased resistance to extinction when rats were trained on 0.25 mg/kg and forced to abstain for 30 versus 15 days. Directionally opposite effects were apparent in groups trained with 0.50 mg/kg. Reinstatement data indicated greater responsivity to cues by animals abstaining for 30 versus 15 days.