RESUMO
Drugs that act to reduce glutamatergic neurotransmission such as NMDA receptor antagonists exert antidepressant-like effects in a variety of experimental paradigms, but their therapeutic application is limited by undesired side effects. In contrast, agents that reduce glutamatergic tone by blocking type I metabotropic glutamate receptors have been suggested to have more a favorable side-effect profile. The present study aimed to compare the effects of mGluR1 antagonist (EMQMCM; JNJ16567083, 3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate, 0.156-10 mg/kg) and mGluR5 antagonist (MTEP, [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine, 1.25-10 mg/kg) in two behavioral screening assays commonly used to assess antidepressant-like activity. In the modified forced swim test in rats, imipramine (used as a positive control) decreased immobility (MED 40 mg/kg) and increased the duration of escape-oriented (climbing and diving; MED 20 mg/kg) behaviors. Both EMQMCM and MTEP decreased the floating duration (MED 1.25 and 2.5 mg/kg) and increased the duration of mobile behaviors (paddling and swimming; MED 2.5 and 5 mg/kg). EMQMCM but not MTEP increased the duration of escape behaviors (climbing and diving; MED 1.25 mg/kg). In the mouse tail suspension test, EMQMCM (5 but not 2.5, 10 and 25 mg/kg), 2-methyl-6-(phenylethynyl)-pyridine (MPEP, 10 but not 1 mg/kg) and MTEP (MED 25 mg/kg) decreased immobility scores. For EMQMCM, the dose-effect relationship was biphasic. With the exception of EMQMCM (10 mg/kg), locomotor activity in mice was not affected by treatments. The present study therefore suggests that acute blockade of mGluR5 and also of mGluR1 exerts antidepressant-like effects in behavioral despair tests in rats and mice.
Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo/psicologia , Elevação dos Membros Posteriores/psicologia , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Natação/psicologia , Animais , Antidepressivos Tricíclicos/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Imipramina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptor de Glutamato Metabotrópico 5 , Tiazóis/farmacologiaRESUMO
Experiments on mice showed that the GABA-positive preparations (THIP, baclofen, fenibut, valproate sodium) intraperitoneally injected in the course of the morphine addiction development (double daily subcutaneous injections at a dose increasing from 10 to 100 mg/kg over a period of 8 days) and, to a greater extent, upon cessation of the morphine injections, partly reduce manifestations of the naloxone-enhanced (0.1 mg/kg, s.c.) daily abstinence, as evaluated by the hopping activity and pair interaction tests.