Biochemical and behavioral changes in rats during and after chronic d-amphetamine exposure.

Two groups of rats were implanted with ALZET minipumps to deliver vehicle or a theoretical amount of 1 mg/kg per h of d-amphetamine (A) for 12 days. After 3 days of A-exposure, motor movements and stereotypic behavior were markedly increased. Subsequent testing during A-exposure showed that motor movements and stereotypic behavior remained significantly increased but declined. After removal of the pumps, these effects disappeared and no differences at rest, during stress or A challenge, were apparent in either group. Animals sacrificed after 3 days of drug exposure, showed a drastic decrease in cardiac, but not adrenal, catecholamine levels. In the brain, norepinephrine (NE) levels were markedly decreased in the frontal cortex, hypothalamus, caudate, pons-medulla and cerebellum. Epinephrine (E) levels were unaffected and dopamine (DA) levels were decreased in most areas without reaching statistical significance. Plasma corticosterone levels were similar in both groups. Animals in both groups sacrificed about 25 days after pump removal were biochemically similar. Under our conditions, A-exposure produced marked behavioral and biochemical changes but there was no evidence of residual abnormalities after cessation of drug treatment.