DECREASED FOREBRAIN [S-35] TBPS BINDING AND INCREASED [H-3] MUSCIMOL BINDING IN RATS THAT DO NOT DEVELOP STRESS-INDUCED BEHAVIORAL DEPRESSION

Recent evidence suggests that anxiety and its biological concomitants may be involved in the pathophysiology of depression. In the present s tudy, the in vitro radioligand binding of [H-3]flunitrazepam, [H-3]mus cimol and [S-35]t-butylbicyclophosphorothionate (TBPS) sites on the be nzodiazepine/GABA Chloride ionophore receptor complex (BGRC) was exami ned using the learned helplessness paradigm. Only rats which did not d evelop the syndrome showed a significant increase in [H-3]muscimol bin ding in cerebral cortex and a decrease in [S-35]TBPS binding in cerebr al cortex and hippocampus in comparison to naive controls. For both li gands, this represented a change in B-max rather than a change in affi nity. Adrenalectomy had no impact on these alterations indicating that critical endogenous factors are not manufactured by the adrenal gland s. These findings suggest that the BGRC in the forebrain may be a site mediating the 'coping' ability of rats that do not develop the learne d helplessness syndrome. The possible involvement of neurosteroids in this effect is discussed.