Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine.
Repeated administration of large doses of d-methamphetamine produce long-lasting depletion of brain dopamine (DA) and serotonin (5-HT), as well as persistent decreases in the activity of their respective biosynthetic enzymes, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). The present results indicate that the inhibitor of 5-HT uptake fluoxetine, prevented the long-term depletion of 5-HT produced by large doses of methamphetamine (15 mg/kg X 5, 6 hr apart) in the neostriatum and hippocampus, while simultaneously augmenting the depletion of DA produced by this drug in the neostriatum. Fluoxetine also enhanced the prolonged neostriatal depletion of DA produced by a comparable regimen of d-amphetamine. In these doses (15 mg/kg X 5,6 hr apart), d-amphetamine did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus. Larger depletion of DA after the amphetamines had been administered in the fluoxetine pretreated animal were associated with a transient increase in the brain levels of methamphetamine and amphetamine. This suggests that fluoxetine may inhibit the metabolism of amphetamines.
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D011437:Propylamines; D005473:Fluoxetine; D012701:Serotonin; D008694:Methamphetamine; D003913:Dextroamphetamine; D004298:Dopamine