Effects of N-ethylmaleimide on dopamine release in the rat striatum after repeated treatment with methamphetamine.
Effects of N-ethylmaleimide or forskolin on electrically evoked dopamine release were investigated in striatal slices of rats pretreated with methamphetamine. N-Ethylmaleimide and forskolin both enhanced the evoked dopamine release in a concentration-dependent manner. The enhancement by N-ethylmaleimide of spontaneous dopamine release was not abolished by tetrodotoxin; the electrically evoked release was abolished, irrespective of its magnitude. Moreover, N-ethylmaleimide prevented the inhibitory effect of the dopamine receptor agonist, 2-amino-6-allyl- 5,6,7,8-tetrahydro-4H-thiazolo(5,4-d)-azepine dihydrochloride (B-HT 920) and the stimulatory effect of the dopamine receptor antagonist, (-)-sulpiride, on the evoked dopamine release. In contrast, forskolin had no effect on the B-HT 920-induced inhibition and (-)-sulpiride-induced enhancement of the evoked dopamine release. These data indicate that release-modulating dopamine autoreceptors are N-ethylmaleimide-sensitive and forskolin-insensitive. As N-ethylmaleimide has been reported to inactivate Gi protein and to block the regulation of noradrenaline release by alpha 2-adrenoceptors, the present results suggest that N-ethylmaleimide inactivates inhibitory GTP binding proteins to block the regulation by dopamine autoreceptors of evoked dopamine release. Methamphetamine pretreatment, which caused behavioral sensitization to a challenge dose of methamphetamine, attenuated the stimulatory effect of N-ethylmaleimide but not forskolin on the evoked dopamine release. The data indicate that the repeated administration of methamphetamine reduces a function of N-ethylmaleimide sensitive signal transduction system, probably including inhibitory GTP binding protein.
Yamada
S
S
Department of Pharmacology, Kurune University School of Medicine, Japan.
Yokoo
H
H
Nishi
S
S
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005033:Ethylmaleimide / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
D001381:Azepines; D015259:Dopamine Agents; D005576:Colforsin; D008694:Methamphetamine; C024763:talipexole; D013469:Sulpiride; D019204:GTP-Binding Proteins; D005033:Ethylmaleimide; D004298:Dopamine