The influence of antidepressive treatment on GABA-related mechanisms in the rat hippocampus: behavioral studies

The effect of antidepressive treatment upon central GABAergic mechanisms has been studied in a behavioral model. Local injections (dentate gyrus of the dorsal hippocampus) of picrotoxin, a chloride channel blocker linked with the function of GABA-A receptor complex, potently stimulated rat motility recorded in the automated open fields. The intra-hippocampal administration of GABA antagonized the behavioral effect of picrotoxin (0.5 microgram). Similar effects were produced by addition to picrotoxin solution (0.25 microgram) of the GABA-A receptor agonist muscimol (0.25 microgram). Chronic (21-day), but not single, treatment of rats with desipramine (10 mg/kg, IP, daily) significantly attenuated picrotoxin-induced locomotor stimulation, when the GABA antagonist was given 24 hr after the last dose of the antidepressant. Repeated electroconvulsive shocks did not significantly change picrotoxin effect, while single shock produced some degree of inhibition of drug-induced motor stimulation. It is hypothesized that chronically applied desipramine, but not electroconvulsive shocks, may enhance the activity of hippocampal GABA-A receptor-related system.