Neurotransmitters, anxiety and benzodiazepines: a behavioral review.

The possible involvement of serotonin, GABA and opioid peptides in anxiety and in the mechanism of action of benzodiazepine tranquilizers have recently been the subjects of intensive biochemical, neurophysiological and behavioral research. The present review examines the behavioral evidence, viewing anxiety and benzodiazepine action as far as possible separately. Four behavioral paradigms of experimental anxiety or "conflict behaviors" are described and assessed for soundness with some practical considerations. The functional significance and pharmacology of benzodiazepine receptors are discussed, and the cases for a number of putative endogenous ligands are examined. Conflict behavior is attenuated by drugs which reduce functional serotonin activity and enhanced by serotonin agonists, but there is little evidence to implicate serotonin in benzodiazepine action. GABA antagonists both intensify conflict and reduce benzodiazepine effects, but evidence of the reverse effects with GABA agonists is more equivocal. The interpretation of behavioral effects of opiate agonists and antagonists and their interactions with benzodiazepines is hindered by their actions on motivational systems other than anxiety, and evidence for an important role of opioid peptides is only suggestive. Some promising lines for future research are indicated.