7-Hydroxy-N,N'-di-n-propyl-2-aminotetraline, a preferential dopamine D3 agonist, induces c-fos mRNA expression in the rat cerebellum.
The effects of a preferential dopamine D3 receptor agonist 7-hydroxy-N,N'-di-n-propyl-2-aminotetralin (7-OH-DPAT) on c-fos mRNA expression in the rat cerebellum were studied by Northern blot analysis. 7-OH-DPAT (0.003-10 mg/kg, s.c.) markedly increased c-fos mRNA expression in the cerebellum, while its effects in the striatum, nucleus accumbens, and frontal cortex were negligible. The effect of 7-OH-DPAT on cerebellar c-fos mRNA expression was dose-dependent and statistically significant at doses of 0.3 mg/kg or more. A preferential dopamine D2 agonist, bromocriptine (0.01-3 mg/kg, s.c.), failed to increase c-fos mRNA expression in the cerebellum. The effect of 7-OH-DPAT was blocked by two dopamine D2-type-receptor antagonists, haloperidol and perospirone, but not the D1-type-receptor antagonist SCH23390. Furthermore, dopaminergic denervation by 6-hydroxydopamine did not inhibit but rather potentiated the 7-OH-DPAT-induced c-fos mRNA expression in the cerebellum. These findings suggest that 7-OH-DPAT increases c-fos mRNA expression in the rat cerebellum, probably through postsynaptic dopamine D3 receptor activation.
Ishibashi
Tadashi
T
Discovery Research Laboratories I, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan. isibasi@sumitomopharm.co.jp
Wakabayashi
Junko
J
Ohno
Yukihiro
Y
D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D016762:Genes, fos / Q000187:drug effects* / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000096:biosynthesis; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C031349:7-hydroxy-2-N,N-dipropylaminotetralin