Mechanism of action of the benzodiazepines: behavioral aspect

The mechanism of action of benzodiazepines is considered from a behavioral pharmacology perspective, particularly with respect to methods that involve suppression of responding, such as the punishment-conflict model. Four biochemical hypotheses of current interrest are reviewed. 1) Several lines of evidence suggest that the benzodiazepine receptor in brain is related to the antianxiety actions of benzodiazepines, including a high correlation between potency in the binding assay and potency in the test, and some novel nonbenzodiazepine compounds that bind to the receptor and are also active in the conflict tests. 2) The evidence is mixed concerning whether inosine or hypoxanthine may be endogenous ligands for the benzodiazepine receptor. Unlike benzodiazepines, neither inosine nor hypoxanthine antagonizes convulsions induced by pentylenetetraxol in the rat. 3) Much research indicates that gamma-aminobutyric acid (GABA) mediates various electrophysiological and biochemical actions of benzodiazepines. Several studies have also found that picrotoxin or bicuculline block the behavior effects of benzodiazepines, although some conflicting results have been reported. Most available findings suggest that GABA agonists, e.g., muscimol, do not exhibit the antianxiety profile of the benzodiazepines. 4) Additional evidence has accumulated to support the hypothesis that the behavioral actions of the benzodiazepines are mediated by serotonin, possibly with the involvement of GABA.