GLUCOCORTICOIDS HAVE STATE-DEPENDENT STIMULANT EFFECTS ON THE MESENCEPHALIC DOPAMINERGIC TRANSMISSION

An increase in the activity of mesencephalic dopaminergic neurons has been implicated in the appearance of pathological behaviors such as ps ychosis and drug abuse, Several observations suggest that glucocortico ids might contribute to such an increase in dopaminergic activity, The present experiments therefore analyzed the effects of corticosterone, the major glucocorticoid in the rat, both on dopamine release in the nucleus accumbens of freely moving animals by means of microdialysis, and on locomotor activity, a behavior dependent on accumbens dopamine, Given that glucocorticoids have certain state-dependent neuronal effe cts, their action on dopamine was studied in situations differing in d opaminergic tonus, including during the light and dark phases of the c ircadian cycle, during eating, and in groups of animals differing in t heir locomotor reactivity to novelty, Dopaminergic activity is increas ed in the dark period, further increased during food-intake, and is hi gher in rats defined as high responders to novelty than in low respond ers, Corticosterone, peripherally administered in a dose that approxim ates stress-induced plasma concentrations, increased extracellular con centrations of dopamine, and this increase was augmented in the dark p hase, during eating, and in high responder rats, Corticosterone had li ttle or no effects in the light phase and in low responder rats. Corti costerone also stimulated locomotor activity, an effect that parallele d the release of dopamine and was abolished by neurochemical (6-hydrox ydopamine) depletion of accumbens dopamine, In conclusion, glucocortic oids have state-dependent stimulant effects on mesencephalic dopaminer gic transmission, and an interaction between these two factors might b e involved in the appearance of behavioral disturbances.