Chronic corticosterone administration enhances behavioral sensitization to amphetamine in mice.
The role of corticosterone (CCS) in regulating sensitization to amphetamine'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 response to amphetamine (sensitization) 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 stereotype 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Pauly
J R
JR
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Robinson
S F
SF
Collins
A C
AC
D000315:Adrenalectomy; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002784:Cholesterol / Q000494:pharmacology; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004343:Drug Implants; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*; D011863:Radioimmunoassay; D013997:Time Factors
D004343:Drug Implants; D002784:Cholesterol; D000661:Amphetamine; D003345:Corticosterone