Further evaluation of the mechanism by which amphetamine reduces striatal dopamine metabolism: a brain dialysis study.

An intracerebral dialysis method was used in the halothane-anaesthetized rat to further clarify the site which mediates the amphetamine-induced decrease of the striatal dopamine (DA) metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Following subcutaneous injection of amphetamine (0.1-5.0 mg/kg), DOPAC and HVA in striatal perfusates decreased over the 2 h time course, with 0.5 mg/kg of the drug having maximal effect. In comparison, amphetamine (0.1-5.0 mg/kg) caused a strictly dose-dependent increase of DA in striatal perfusates. Following low (0.1-5.0 mg/kg) but not high (2.0-5.0 mg/kg) doses of amphetamine there was a negative correlation between the increase of DA and decrease of DOPAC in the striatum. Amphetamine (0.5 mg/kg) caused a reduction in DA metabolism in the ibotenic acid-lesioned striatum. Intranigral injection of 10 micrograms, but not of 1 microgram amphetamine, decreased DOPAC (-27%) in the striatal perfusates. However, injection of 1 microgram amphetamine into the striatum caused a strong decrease in striatal DOPAC (-46%) and HVA (-22%). The possible mechanisms of action of amphetamine are discussed in the light of these data.