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.
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D007051:Ibotenic Acid; D007267:Injections; D008297:Male; D010648:Phenylacetates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra
D010648:Phenylacetates; D007051:Ibotenic Acid; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid