Chronic corticosterone administration enhances behavioral sensitization to amphetamine in mice

The role of corticosterone (CCS) in regulating sensitization to ampetamine's locomotor activating effects was measured in female DBA/2 mice that had been sham-operated or adrenalectomized and implanted with CCS-containing or cholesterol pellets. Three days following surgery, the mice were injected with saline and circular open field locomotor activity was measured for a 5-min time period starting 15 min after injection. Over the next 4 days, amphetamine (1.0-10.0 mg/kg) was injected and locomotor response measured. Control animals (sham-operated, cholesterol pellet) showed increased locomotor activity following their first 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 responsiveness to amphetamine in either sham-operated or ADX animals, but it did alter the dose-dependent sensitization to amphetamine. Both sham-operated and ADX animals implanted with cholesterol pellets showed increased locomotor respponse to amphetamine (sensitation) following injection with 2.5, 5.0 and 10.0 mg/kg doses of amphetamine. However, the enhancement of locomotor activity was greater in the sham-operated control animals. CCS-treated sham-operated animals exhibited sensitization to the locomotor-activating effects of amphetamine at the lowest dose used (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 the 2.5 mg/kg dose, and showed sensitization to amphetamine-induced stereotypy at higher doses. These data demonstrate that adrenocortical status modulates the effects of chronic and acute amphetamine administration and suggest that CCS may be an important component of stress-induced alterations in amphetamine sensitivity.