RESUMO
The noradrenaline, serotonin and dopamine transporters are three main transporters, which are the target of the antidepressant drugs. In the present study we demonstrate that the life-long deletion of the noradrenaline transporter (NET) induced up-regulation of two other monoamine transporters, dopamine and serotonin (DAT and SERT, respectively). An increase in the binding of [(3)H]paroxetine to the SERT and [(3)H]GBR12935 to the DAT was observed in various brain regions of NET-KO mice, without alterations of mRNA encoding these transporters, as measured by in situ hybridization. This important finding impacts the interpretation of previous data indicating the supersensitizity of NET-KO mice for psychostimulants or stronger effect of citalopram in behavioral tests. While using the NET-KO mice in various psychopharmacological studies is very important, one has to be aware that these mice lack NET from the earliest period of their existence, thus compensatory alterations do take place and have to be considered when it comes to interpretation of the obtained results.
Assuntos
Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/fisiologia , Receptores de Serotonina/metabolismo , Regulação para Cima , Animais , Autorradiografia , Sequência de Bases , Primers do DNA , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Hibridização In Situ , Masculino , Camundongos , Camundongos Knockout , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Paroxetina/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Receptores de Serotonina/genéticaRESUMO
In the present study, we investigated plasma corticosterone levels of genetically modified mice lacking noradrenaline transporter (NET(-/-)), in response to the forced swim test (FST) and tail suspension test (TST). FST strongly increased the plasma corticosterone level in the first minute after the test (significantly only in NET(+/+) mice), while TST was without any significant effect in both genotypes studied. A single dose of tianeptine (20 mg/kg, ip) shortened immobility time in both tests in NET(-/-) mice, as well as NET(+/+) mice subjected to FST, but not TST. The lack of effect of tianeptine in control animals (NET(+/+)) subjected to TST is also reflected in unchanged levels of plasma corticosterone.
Assuntos
Corticosterona/sangue , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/fisiologia , Animais , Feminino , Fenclonina/farmacologia , Elevação dos Membros Posteriores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Natação , Tiazepinas/farmacologiaRESUMO
The present study examined the effect of citalopram (7.5 and 15 mg/kg) in the modified forced swim test (FST) in Wistar rats, in comparison to the effect of desipramine at the same doses. The citalopram at both doses increased swimming behavior, at the cost of climbing and immobility. The administration of desipramine increased climbing behavior while immobility counts were decreased. The modified FST is indeed more sensitive than the conventional FST in describing precisely the behavioral effects of antidepressant drugs, allowing to roughly estimate the contribution of individual neurotransmitter system to the mechanism of action of the studied drug.