The effects of compounds related to gamma-aminobutyrate and benzodiazepine receptors on behavioural responses to anxiogenic stimuli in the rat: choice behaviour in the T-maze.

Two methods were used to test rats' responses to novelty in the T-maze: (1) a test of spontaneous alternation allowing separate measurement of place and body turn alternation; and (2) a test of entry into an arm of changed brightness ("response to stimulus change"). Chlordiazepoxide reduced spontaneous alternation by specifically weakening body turn alternation and eliminated the response to stimulus change. These findings are similar to those previously reported for the barbiturate sodium amylobarbitone. The same pattern of change in the two tests was seen after a low dose of the GABAA agonist muscimol (0.00125 mg/kg); when the dose of muscimol was raised (0.01 and 0.25 mg/kg), place alternation was also reduced. Picrotoxin but not bicuculline (both GABAA blockers) reversed the effects of muscimol and partially those of chlordiazepoxide on the response to stimulus change; in the spontaneous alternation test picrotoxin only marginally affected the response to 0.25 mg/kg muscimol and actually enhanced the effect of 0.000125 mg/kg. The GABAB agonist baclofen (1 mg/kg) acted in the test of response to stimulus change like chlordiazepoxide and muscimol; however, when baclofen was combined with muscimol, the two drugs tended to show mutual blocking. These results are generally consistent with the hypothesis that GABAergic mechanisms play a role in anxiolytic behavioural activity, but many details are difficult to explain.