Behavioral sensitization to amphetamine is dependent on corticosteroid receptor activation.

Thirty rats received 3 amphetamine injections (1.5 mg/kg, s.c.) 6 days apart and the locomotor response was measured. One day before the second injection they were adrenalectomized or sham operated. Corticosteroid replacement treatments (500 micrograms/kg, s.c.) were given every evening. Sham adrenalectomized animals exhibited behavioral sensitization to successive injections of amphetamine, which was prevented by adrenalectomy. Treatment with corticosterone or deoxycorticosterone did not reverse the effect of adrenalectomy, whereas dexamethasone completely restored and even potentiated sensitization to amphetamine. These results demonstrate that corticosteroids are necessary for sensitization of the dopaminergic system to occur and that they most probably act through the type II (or glucocorticoid) receptor subtype.