Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine

Abstract

Studies of intravenous self-administration and psychomotor effects of drugs have recently suggested that stress-induced corticosterone secretion may be an important factor determining vulnerability to drugs of abuse. In this report, we studied if basal physiological corticosterone secretion modulates sensitivity to cocaine and morphine, and if changes in the reactivity of mesolimbic dopaminergic (DA) neurons, one of the principal substrates of drug-reinforcing effects, are involved. For this purpose we determined the psychomotor effects of these drugs in animals in which corticosterone secretion was suppressed by adrenalectomy and in adrenalectomized animals submitted to different corticosterone replacement therapies designed to mimic (1) only the diurnal levels of the hormone, obtained by the subcutaneous implantation of 50 mg corticosterone pellets; (2) only the nocturnal levels, obtained by adding corticosterone (50 μg/ml) to the drinking solution during the dark period; and (3) the entire circadian fluctuation, obtained by combining the two previous treatments. Locomotor response to cocaine and morphine was studied after both systemic and central injections, into the nucleus accumbens for cocaine and into the ventral tegmental area for morphine. These sites were chosen because stimulant effects of cocaine and morphine injected in these structures are dopamine dependent. Our results show that suppression of corticosterone by adrenalectomy reduced the locomotor response to cocaine and morphine, injected both systemically and centrally. The reinstatement of diurnal levels of corticosterone totally reversed adrenalectomy's effects on the behavioral response to cocaine, whereas the reestablishment of the entire corticosterone circadian fluctuation (diurnal plus nocturnal levels) was necessary to reverse the response to morphine. In conclusion, our results indicate that physiological corticosterone secretion facilitates dopamine-mediated locomotor effects of cocaine and morphine. Since stimulant effects and activation of DA mesencephalic neurons by these drugs are related to their reinforcing properties, an interaction between corticosterone and dopamine may be part of the pathophysiological mechanism underlying vulnerability to drug abuse.