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J Neurosci Res ; 68(4): 470-8, 2002 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-11992474

RESUMO

We reported previously that (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole hydrochloride (MKC-242) (3 mg kg(-1), i.p.), a selective 5-HT(1A) receptor agonist, accelerated the re-entrainment of hamster wheel-running rhythms to a new 8 hr delayed or advanced light-dark cycle, and also potentiated the phase advance of the wheel-running rhythm produced by light pulses. The molecular mechanism underlying MKC-242-induced potentiation of this phase shift, however, has not yet been elucidated. We examined the effects of MKC-242 on light-induced mPer1 and mPer2 mRNA expression in the suprachiasmatic nucleus (SCN) of mice. MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced mPer1 and mPer2 expression in the SCN of mice housed in constant darkness for 2 days, when mRNA levels were observed 3 hr after light-exposure. More potentiating action of MKC-242 on mPer2 expression in the SCN was observed in mice housed in constant darkness for 9-10 days. This facilitatory action of MKC-242 on mPer1 expression was antagonized by WAY100635, a selective 5-HT(1A) receptor blocker, indicating that MKC-242 activated 5-HT(1A) receptors. Other drugs such as 8-hydroxy-dipropylaminotetralin (10 mg kg(-1), i.p.), paroxetine (10 mg kg(-1), i.p.), buspirone (10 mg kg(-1), i.p.), and diazepam (10 mg kg(-1), i.p.) did not display a potentiating action on light-induced mPer1 and mPer2 expression in the SCN. In the behavioral experiments, we found that MKC-242 (5 mg kg(-1), i.p.) potentiated light-induced phase delays of free-running rhythm in mice. The present results suggest that prolonged increase of mPer1 or mPer2 expression in the SCN by MKC-242 may be involved in the potentiation of photic entrainment by MKC-242 in mice.


Assuntos
Dioxanos/farmacologia , Dioxóis/farmacologia , Luz , Proteínas Nucleares/biossíntese , Receptores de Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologia , Núcleo Supraquiasmático/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Buspirona/farmacologia , Proteínas de Ciclo Celular , Ritmo Circadiano , Diazepam/farmacologia , Dioxanos/antagonistas & inibidores , Dioxóis/antagonistas & inibidores , Moduladores GABAérgicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hibridização In Situ , Masculino , Camundongos , Atividade Motora , Proteínas Nucleares/genética , Paroxetina/farmacologia , Proteínas Circadianas Period , Piperazinas/farmacologia , Piridinas/farmacologia , RNA Mensageiro/análise , Receptores 5-HT1 de Serotonina , Antagonistas da Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Fatores de Transcrição
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