Decreased forebrain [³⁵S]TBPS binding and increased [³H]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 study, the in vitro radioligand binding of [³H]flunitrazepam, [³H]muscimol and [³⁵S]t-butylbicyclophosphorothionate (TBPS) sites on the benzodiazepine /GABA chloride ionophore receptor complex (BGRC) was examined using the learned helplessness paradigm. Only rats which did not develop the syndrome showed a significant increase in [³H]muscimol binding in cerebral cortex and a decrease in [³⁵S]TBPS binding in cerebral cortex and hippocampus in comparison to naive controls. For both ligands, this represented a change in B_max rather than a change in affinity. Adrenalectomy had no impact on these alterations indicating that critical endogenous factors are not manufactured by the adrenal glands. These findings suggest that the BGRC in the forebrain may be a site mediating the 'coping' ability of rats that do not develop the learned helplessness syndrome. The possible involvement of neurosteroids in the effect is discussed.