CHRONIC CORTICOSTERONE ADMINISTRATION ENHANCES BEHAVIORAL SENSITIZATION TO AMPHETAMINE IN MICE

The role of corticosterone (CCS) in regulating sensitization to amphet amine's locomotor activating effects was measured in female DBA/2 mice that had been sham-operated or adrenalectomized and implanted with CC S-containing or cholesterol pellets. Three days following surgery, the mice were injected with saline and circular open field locomotor acti vity was measured for a 5-min time period starting 15 min after inject ion. Over the next 4 days, amphetamine (1.0-10.0 mg/kg) was injected a nd locomotor response measured. Control animals (sham-operated, choles terol pellet) showed increased locomotor activity following their firs t injection of 5.0 mg/kg and 10.0 mg/kg amphetamine, while ADX animals showed increased activity only after treatment with the 10 mg/kg dose . Chronic CCS treatment did not significantly alter initial responsive ness to amphetamine in either sham operated or ADX animals, but it did alter the dose-dependent sensitization to amphetamine. Both sham-oper ated and ADX animals implanted with cholesterol pellets showed increas ed locomotor response to amphetamine (sensitization) following injecti on with 2.5, 5.0 and 10.0 mg/kg doses of amphetamine. However, the enh ancement of locomotor activity was greater in the sham-operated contro l animals. CCS-treated sham-operated animals exhibited sensitization t o the locomotor-activating effects of amphetamine at the lowest dose u sed (1.0 mg/kg) and increased stereotypy following treatment with the higher doses. ADX/CCS animals developed sensitization to the locomotor -activating effects of amphetamine following chronic injection with th e 2.5 mg/kg dose, and showed sensitization to amphetamine-induced ster eotypy at higher doses. These data demonstrate that adrenocortical sta tus modulates the effects of chronic and acute amphetamine administrat ion and suggest that CCS may be an important component of stress-induc ed alterations in amphetamine sensitivity.