Behavioral differences in an elevated plus-maze: correlation between anxiety and decreased number of GABA and benzodiazepine receptors in mouse cerebral cortex.

Abstract

In an elevated plus-maze model of anxiety mice treated with the benzodiazepine inverse agonist DMCM (0.5-1.5 mg/kg i.p.) spent significantly less time on the open arms and showed the decreased number of open arm entries. The opposite i.e. increased time spent on the open arms and the higher number of open arm entries was registered after diazepam (1.5 mg/kg). The results are consistent with the results obtained in the other animal tests and support the idea that this procedure is suitable for detecting anxiolytic/anxiogenic effects of benzodiazepine receptor ligands. After testing of 84 mice in an elevated plus-maze substantial differences were detected between the individuals. According to the behavioral response two subgroups of animals with DMCM or diazepam like exploratory activity (as compared to the whole group data) termed as "anxious" or "non-anxious", respectively, were chosen for further binding studies. "Anxious" animals had significantly lower numbers of 3H-flunitrazepam and 3H-muscimol binding sites as compared to "non-anxious" animals in cerebral cortex but not in cerebellum. No differences in the affinity were found between the two groups studied. The results indicate that behavioral anxiety in mice is in correlation with the decreased number of GABA and benzodiazepine receptors in cerebral cortex.