Involvement of benzodiazepine recognition sites in the foot shock-induced decrease of low affinity GABA receptors in...

The cerebral cortices of rats habituated to the handling manipulation that precedes sacrifice by guillotine (unstressed rats) have a higher number of low affinity GABA receptors than naive rats (stressed rats). Foot shock stress delivered to handling-habituated rats 5 min before sacrifice decreased the number of low affinity GABA receptors to the level found in naive animals, while leaving almost unchanged the [3H]GABA binding in the latter group. Since benzodiazepine (BZ) recognition sites are the target through which benzodiazepines modulate the emotional states of the animals, we investigated whether these receptors were involved in the action of foot shock stress on GABA binding. The in vitro addition of diazepam (5 X 10(-6) M) to cortical membranes from foot-shocked handling-habituated rats brought back the number of low affinity GABA receptors to the level found in cortical membranes from handling habituated rats. Moreover, the effect of foot shock on low affinity GABA receptors was completely antagonized in vivo by pretreatment with the specific benzodiazepine antagonist Ro15-1788 (30 mg/kg per os). Since the effect of foot shock on [3H]GABA binding is mimicked by the in vitro addition of beta-carbolines to cortical membranes from handling habituated rats, our working hypothesis is that an endogenous ligand for BZ recognition sites, possessing beta-carboline-like properties, is released during foot shock stress.