Conditioned rewarding stimulus associated with cocaine self-administration reverses the depression of catecholamine brain systems following cocaine withdrawal in rats.

Craving phenomena are related to induction of substance-seeking behaviour by stimuli associated with the availability of the drug. We investigated the changes in monoamine metabolism in regions of the brains of rats that, following a period of training of cocaine self-administration, were either killed 2 h after the last session or underwent extinction trials, during which cocaine was withdrawn. During the training, acoustic and visual stimuli announced the availability of cocaine. After 10 d of daily extinction trials, rats were re-introduced into the cage, and a signal associated with cocaine availability was applied to half of the animals. The rats were immediately killed and concentrations of dopamine and serotonin and their metabolites in various brain areas, and the concentration of noradrenaline and MHPG in the brainstem were assessed to calculate their metabolism rate indices. In rats self-administering cocaine, the levels of metabolites of all three amines were depressed, indicating a depression of the activity of monoaminergic systems. In the period of extinction, the dopamine levels in the nucleus accumbens and striatum and the level of the noradrenaline metabolite, MHPG, in the brainstem were reduced, suggesting a long-lasting disturbance of the catecholaminergic system, while serotonin levels and metabolism returned to normal values. The presence of the signal associated with previous cocaine availability, which invariably caused the reinstatement of cocaine-seeking behaviour annulled the changes observed in the group receiving no stimulus, bringing the concentration values of dopamine, and dopamine and noradrenaline metabolites to yoked-saline control rats. The results suggest that the stabilized self-administration of cocaine depresses the activity of all biogenic amine systems, and the changes in serotonin system are reversible, in contrast to those observed in catecholaminergic systems, which show the signs of a long-lasting impairment. The stimulus associated with cocaine availability activates the catecholaminergic system in animals after extinction procedure.