The Benzodiazepine—GABA Receptor Complex in Experimental Stress, Anxiety and Depression

Abstract

Benzodiazepine receptors mediate many of the pharmacological actions of the benzodiazepines and related minor tranquillisers, including their anxiolytic, hypnotic and muscle-relaxant properties (see Tallman et al., 1980; Skolnick and Paul 1982 for review). The benzodiazepine receptor or recognition site is part of an oligomeric glycoprotein receptor complex for the major inhibitory neuro-transmitter in brain, γ-aminobutyric acid (GABA). Benzodiazepines and barbiturates augment GABAergic neurotransmission by binding to different allosteric binding sites on this receptor complex, resulting in a potentiation of GABA-receptor-mediated Cl− ion conductance (Olsen et al., 1984). More recently, a class of compounds referred to as inverse agonists have been discovered and shown to bind to the benzodiazepine receptor to produce ‘anxiogenic’ and pre-convulsant actions (Ninan et al., 1982; Dorow et al., 1983; Insel et al., 1984). The latter finding suggests that the benzodiazepine-GABA receptor complex may participate in the neurochemical events which mediate the physiological (and perhaps psychological) expression of anxiety or fear. One obvious question, therefore, is whether the benzodiazepine-GABA receptor is itself modified by environment stimuli, and whether such modifications are important to the organism’s adaptive response to ‘stress’. Most studies which have examined for the effects of environmental or experimentally induced ‘stress’ on the benzodiazepine receptor complex have reported either no, or very modest, changes in the ligand binding characteristics of these receptors (e.g. see Braestrup et ah, 1979; Grimm and Hershkowitz, 1981).