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Eur J Pharmacol ; 471(1): 21-6, 2003 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-12809948

RESUMO

This study examined the effects of peripheral-type benzodiazepine receptors in the forced swimming test. PK 11195 (1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-isoquinoline carboxamide) and Ro5-4864 (7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine-2-one) were i.p. injected in mice, according to an acute (1 or 24 h) and a repeated (14 days) schedule. Pretreatment with the agonist, Ro5-4864, significantly reduced immobility time 1 h after treatment but not 24 h after it, whereas the antagonist, PK11195, did not interfere with the test parameters. Nevertheless, PK11195 pretreatment inhibited the Ro5-4864 antidepressant-like effect. Animals repeatedly treated with Ro5-4864 had a similar profile of action with no sign of motor impairment or locomotor activation as evaluated in the rota-rod and open-field tests, respectively. Aminoglutethimide pretreatment, which blocks the early step of steroid synthesis, inhibited the antidepressant-like effect of Ro5-4864. The present findings suggest an antidepressant-like profile for the benzodiazepine, Ro5-4864, that seems to involve steroid synthesis as underlying mechanism.


Assuntos
Antidepressivos/farmacocinética , Benzodiazepinas/farmacocinética , Benzodiazepinonas/farmacocinética , Receptores de GABA-A/efeitos dos fármacos , Natação , Aminoglutetimida/administração & dosagem , Aminoglutetimida/farmacocinética , Animais , Antidepressivos/administração & dosagem , Benzodiazepinas/administração & dosagem , Benzodiazepinas/antagonistas & inibidores , Benzodiazepinonas/administração & dosagem , Agonistas de Receptores de GABA-A , Imipramina/administração & dosagem , Imipramina/farmacocinética , Imobilização , Injeções Intraperitoneais , Isoquinolinas/administração & dosagem , Isoquinolinas/farmacocinética , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Sistema Nervoso Periférico/química , Teste de Desempenho do Rota-Rod , Fatores de Tempo
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