RESUMO
To date, very little information is available about the regulation of vesicular monoamine transporter in central serotonergic regions. The expression of the vesicular monoamine transporter 2 (VMAT2) has been studied in the serotonergic system of the rat brain after an 18 day treatment with the serotonin selective-reuptake inhibitor paroxetine (10 mg/kg, i.p., once daily). This treatment, while increasing serotonergic transmission, did not modify either VMAT2 mRNA expression or (3)H-dihydrotetrabenazine binding site density in any of the studied regions. These results suggest that VMAT2 regulation in the central serotonergic system is not involved in the mechanism of action of antidepressants. In addition, a single administration of reserpine (5 mg/kg, s.c.), while blocking the vesicular monoamine uptake function, had no effect on VMAT2 immunoreactivity in the dorsal raphe nucleus 2 or 30 days after injection. It is concluded that neither a reduction (reserpine) nor an enhancement (paroxetine) of the serotonin transmission induces VMAT2 regulation in serotonergic system in the rat brain.
Assuntos
Encéfalo/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras , Neuropeptídeos , Paroxetina/farmacologia , Reserpina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Serotonina/metabolismo , Animais , Autorradiografia , Sítios de Ligação , Transporte Biológico , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Citalopram/metabolismo , Dopamina/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Técnicas In Vitro , Ligantes , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Norepinefrina/metabolismo , Paroxetina/administração & dosagem , Núcleos da Rafe/efeitos dos fármacos , Núcleos da Rafe/metabolismo , Ratos , Ratos Sprague-Dawley , Tetrabenazina/análogos & derivados , Tetrabenazina/metabolismo , Proteínas Vesiculares de Transporte de Aminas Biogênicas , Proteínas Vesiculares de Transporte de MonoaminaRESUMO
We have compared the effects of an i.p. pretreatment with L-DOPA (200 mg/kg) associated with benserazide (25 mg/kg) on neurotoxic effects of either 6-hydroxydopamine (6-OHDA) (50 microg, 10 microl per mouse) or 1-methyl-4-phenylpyridinium (MPP+) (17.5 microg, 10 microl per mouse). The striatal dopamine (DA) content, the vesicular monoamine transporter (VMAT2) density, as well as the hypothalamic norepinephrine (NE) content were measured 8 days after treatments. The L-DOPA-benserazide pretreatment worsened by 65% the 6-OHDA-induced depletion in striatal DA. On the contrary, it reduced by 42% the MPP+-induced depletion in striatal DA and by 54% the MPP+-induced decrease in VMAT2 density. It was noticed that the L-DOPA-benserazide pretreatment did not modify the marked decrease in hypothalamic NE content induced by 6-OHDA.
