Data/hora: 10/06/2024 11:04:57

Provedor de dados: | Brazilian Journal of Medical and Biological Research
País: | Brazil
Título: | Evidence of interaction between fluoxetine and isosorbide dinitrate on neuroleptic-induced catalepsy in mice
Autores: | Pires,J.G.P.; Fonseca,F.C.G.; Woelffel,A.B.; Futuro-Neto,H.A.
Data: | 1998-03-01
Ano: | 1998
Palavras-chave: | Fluoxetine; Isosorbide dinitrate; Neuroleptic-induced catalepsy; Nitric oxide; Serotonin reuptake inhibitors; Dopaminergic transmission.
Resumo: | Drugs which influence 5-HTergic mechanisms can modify neuroleptic-induced catalepsy (NC) in rodents, a phenomenon produced by striatal dopamine (DA) receptor blockade. Previous research also suggests a role for endogenous nitric oxide (NO) in the modulation of striatal DAergic neurotransmission; in addition, NO seems to play a role in the 5-HT reuptake mechanism. It is known that clomipramine potentiates NC in mice, but the reported effects of selective 5-HT reuptake inhibitors (SSRIs) in this model are rather contradictory. We then decided to re-address this issue, investigating the effect of fluoxetine (FX), an SSRI, on NC. In view of the ubiquitous role of NO as a central neuromodulator, we also studied the effect of isosorbide dinitrate (ID), a centrally active NO donor, and how both drugs interact to affect the phenomenon of NC. Catalepsy was induced in male albino mice with haloperidol (H; 1 mg/kg, ip) and measured at 30-min interval by means of a bar test. Drugs (FX, ID and FX + ID) or saline (controls) were injected ip 30 min before H, with each animal used only once. FX (5 mg/kg) significantly reduced NC, with maximal attenuation (about 74%) occurring at 150 min after H. ID (5 mg/kg) also inhibited NC (150 min: 62% attenuation). The combined drugs (FX + ID group), however, caused a great potentiation of NC (4.7-fold at its maximum, at 90 min). The effect observed with ID is compatible with the hypothesis that NO increases DA release in the striatum. The attenuation of NC observed with FX may be due to a preferential net effect on the raphe somatodendritic synapse, where inhibitory 5-HT1A autoreceptors are operative. The enhancement of NC caused by combined administration of FX and ID suggests the presence of a pharmacodynamic interaction, whose mechanism, still unclear, may be related to a decrease in striatal DA release
Tipo: | Info:eu-repo/semantics/article
Idioma: | Inglês
Identificador: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1998000300014
Editor: | Associação Brasileira de Divulgação Científica
Relação: | 10.1590/S0100-879X1998000300014
Formato: | text/html
Fonte: | Brazilian Journal of Medical and Biological Research  v.31 n.3 1998
Fonte: | info:eu-repo/semantics/openAccess