GABAergic modulation of learned helplessness.

Previous studies have demonstrated the GABAergic system in the hippocampus to be a major controlling factor in the reversal of learned helplessness by antidepressants. In the present work, animals in which learned helplessness (LeH) was induced by exposure to uncontrollable electric shock demonstrated a decreased depolarization-induced release of GABA relative to controls, and an increased release of hippocampal glutamate. Injection of bicuculline but not glutamate into the hippocampus produced a behavioral state identical to that induced by uncontrollable shock, but had no influence on pain sensitivity. When flux through the "small" hippocampal pool of GABA was determined, chronic treatment with imipramine or iprindole, but lorazepam or chlorpromazine elevated this measure. These three findings along with those of prior experiments, suggest a controlling role for GABA in the learned helplessness model of depression.