Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine

• Published in: Neuropharmacology Vol. 22; no. 10; p. 1165
• Main Authors: Ricaurte, G A, Fuller, R W, Perry, K W, Seiden, L S, Schuster, C R
• Format: Journal Article
• Language: English
• Published: England 01-10-1983
• Subjects: Animals; Caudate Nucleus - drug effects; Caudate Nucleus - metabolism; Dextroamphetamine - pharmacology; Dopamine - metabolism; Drug Interactions; Fluoxetine - pharmacology; Male; Methamphetamine - pharmacology; Propylamines - pharmacology; Putamen - drug effects; Putamen - metabolism; Rats; Rats, Inbred Strains; Serotonin - metabolism
• ISSN: 0028-3908
• DOI: 10.1016/0028-3908(83)90075-8

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.