Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy

Abstract

Rats exposed to inescapable tailshock exhibit deficits in learning a simple shuttle☐ escape task 24 h later. This syndrome has been termed ‘behavioral depression’ or ‘learned helplessness’, and is a model of stress-induced depression. In the present study a significant (25%) decrease in GABA receptor-mediated chloride ion flux as measured by muscimol-stimulated 36Cl − uptake in synaptoneurosomes was found in the cerebral cortices of rats that failed the shuttle☐ task as compared to naive control rats. Rats which were exposed to tailshock and subsequently learned the escape task did not show a significant difference in muscimol-stimulated 36Cl − uptake as compared to naive control rats. Similarly, rats that failed to learn the shuttle☐ escape task had significantly lower in vivo [ 3H]Ro15-1788 specific binding in cerebral cortex (43%), hippocampus (35%) and striatum (33%) as compared to naive control rats. In cerebellum and hypothalamus, there were significant reductions in specific [ 3H]Ro15-1788 binding in both animals that failed and animals that learned the shuttle☐ escape task as compared to naive controls. To control the stress of the footshock associated with the shuttle☐ escape task, we investigated the effect of gridshock in which total footshock received was equivalent to that received by rats who failed the shuttle☐ task. There were no differences in muscimol-stimulated 36Cl − uptake or in vivo [ 3H]Ro15-1788 specific binding between naive controls and rats administered footshock independent of a learning task. These data suggest that the development of stress-induced behavioral depression may be associated with a decrease in GABA receptor-mediated chloride channel function.