Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens in rats responding on a concurrent schedule of food, water and intravenous morphine self-administration.

The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous self-administration was assessed in rats responding on a concurrent schedule of food, water and morphine presentations. Five rats were trained on a concurrent fixed-ratio schedule of food and water presentation. They were then implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and allowed to choose between intravenous morphine, food and water deliveries. A three-lever choice procedure provided almost continuous access to the three reinforcers. Dose-effect curves were determined by the substitution of the daily dose of morphine (3.3 mg/injection) with other doses (0.83-13.2 mg/injection) or eliminating drug injections (extinction) for 24 hour periods. The behavioral effects of 24 hour food extinction probes were also determined. The rats subsequently received bilateral microinjections of either the vehicle or 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Following the lesion, response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection. The animals were placed back on the concurrent schedule and morphine dose-effect curves were redetermined. The 5,7-DHT lesion resulted in a significant dose-related decrease in morphine self-administration, and little or no effect on responding maintained by food or water presentations. Serotonergic innervations of the nucleus accumbens appear to participate in the neuronal activity mediating intravenous morphine self-administration.