CORTICOSTERONE CIRCADIAN SECRETION DIFFERENTIALLY FACILITATES DOPAMINE-MEDIATED PSYCHOMOTOR EFFECT OF COCAINE AND MORPHINE

Studies of intravenous self-administration and psychomotor effects of drugs have recently suggested that stress-induced corticosterone secre tion may be an important factor determining vulnerability to drugs of abuse. In this report, we studied if basal physiological corticosteron e secretion modulates sensitivity to cocaine and morphine, and if chan ges in the reactivity of mesolimbic dopaminergic (DA) neurons, one of the principal substrates of drug-reinforcing effects, are involved. Fo r this purpose we determined the psychomotor effects of these drugs in animals in which corticosterone secretion was suppressed by adrenalec tomy and in adrenalectomized animals submitted to different corticoste rone replacement therapies designed to mimic (1) only the diurnal leve ls of the hormone, obtained by the subcutaneous implantation of 50 mg corticosterone pellets; (2) only the nocturnal levels, obtained by add ing corticosterone (50 mu g/ml) to the drinking solution during the da rk period; and (3) the entire circadian fluctuation, obtained by combi ning the two previous treatments. Locomotor response to cocaine and mo rphine was studied after both systemic and central injections, into th e nucleus accumbens for cocaine and into the ventral tegmental area fo r morphine. These sites were chosen because stimulant effects of cocai ne and morphine injected in these structures are dopamine dependent. O ur results show that suppression of corticosterone by adrenalectomy re duced the locomotor response to cocaine and morphine, injected both sy stemically and centrally. The reinstatement of diurnal levels of corti costerone totally reversed adrenalectomy's effects on the behavioral r esponse to cocaine, whereas the reestablishment of the entire corticos terone circadian fluctuation (diurnal plus nocturnal levels) was neces sary to reverse the response to morphine. In conclusion, our results i ndicate that physiological corticosterone secretion facilitates dopami ne-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 corti costerone and dopamine may be part of the pathophysiological mechanism underlying vulnerability to drug abuse.