Role of endogenous dopamine in the neurochemical deficits induced by methcathinone.
Multiple administrations of methcathinone caused persistent deficits in monoaminergic systems, as reflected by decreases in dopamine and 5-hydroxytryptamine uptake capacity, tissue content and associated rate-limiting synthetic enzyme activities. Because dopamine has been implicated in mediating such effects after administration of related amphetamine analogs, its role in effecting methcathinone-induced monoaminergic neuronal impairment was assessed. A single high-dose administration of methcathinone increased striatal dopamine release, as measured by microdialysis in conscious rats and reflected by increases in striatal neurotensin-like immunoreactivity. Dopaminergic deficits observed 18 hr after a multiple-dose treatment with methcathinone were prevented by pretreatment with the selective D1 antagonist SCH23390 and D2 receptor antagonist eticlopride, but 5-hydroxytryptaminergic deficits were not altered. 5-Hydroxytryptaminergic changes did not occur in animals depleted of striatal dopamine by 6-hydroxydopamine lesions. These results indicate that dopaminergic systems are profoundly affected by methcathinone administration and that dopamine likely contributes to the monoaminergic effects of this stimulant.
Gygi
M P
MP
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, USA.
Fleckenstein
A E
AE
Gibb
J W
JW
Hanson
G R
GR
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D009496:Neurotensin / Q000032:analysis; D016627:Oxidopamine / Q000494:pharmacology; D011427:Propiophenones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001552:Benzazepines; D011427:Propiophenones; C047806:monomethylpropion; D009496:Neurotensin; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase; D004298:Dopamine