THE ROLE OF CORTICOSTEROIDS IN THE ACQUISITION OF SENSITIZATION TO LOCOMOTOR STIMULANT EFFECTS OF MK-801

In the present study, we investigated the role of corticosterone and g lucocorticoid receptors in the acquisition of sensitization to locomot or stimulant effects of MK-801 in rats. MK-801 (two doses, 0.4 mg/kg i .p. each, given twice, 48 h apart) evoked sensitization, observed as e nhancement of the locomotor activity to a challenging dose of MK-801 ( 0.4 mg/kg) but not of a stereotypy-like activity. Pharmacological mani pulations which deplete endogenous corticosterone, i.e., administratio n of the corticosterone synthesis inhibitor metyrapone (two injections , 150 and 50 mg/kg, given at 24 and 2 h before the first injection of MK-801, 4 mg/kg) or blockade of glucocorticoid receptors by administra tion of the antiglucocorticoid RU 38486 (20 mg/kg, 45 min before MK-80 1, 0.4 mg/kg) abolished the acquisition of sensitization. The obtained results indicate that the endogenous corticosterone and glucocorticoi d receptors (type II) are involved in the acquisition of sensitization to locomotor stimulant effects of MK-801. Final experiments showed th at MK-801 in doses used in the present study (0.4 mg/kg) enhanced the plasma concentration of corticosterone and that single injection of ex ogenous corticosterone (10 mg/kg s.c.) enhanced the locomotor stimulan t effects of MK-801 (0.2 mg/kg). The obtained data indicate that the a cquisition of sensitization to locomotor stimulant effects of MK-801 i nvolves secretion of corticosteroids which probably act through glucoc orticoid receptors, as was found previously for amphetamine and its co ngeners.