Influence of 5-HT1A receptor antagonism on plus-maze behaviour in mice. I. Pindolol enantiomers and pindobind 5-HT1A.

Studies on the behavioural effects of 5-hydroxytryptamine receptor subtype 1A (5-HT1A) antagonists may provide important clues to the precise role of 5-HT1A receptor mechanisms in anxiety. In the first of a series of experiments designed to address this issue, the effects of mixed 5-HT1A and beta-adrenergic receptor antagonists pindolol enantiomers and pindobind 5-HT1A and of metoprolol and ICI 118,551 (selective beta1- and beta2-adrenoceptor antagonists, respectively) were assessed in the mouse elevated plus-maze using ethological techniques. Results showed that, at lower doses, (-)pindolol (0.1-1.6 mg/kg) and pindobind 5-HT1A (0.1-0.5 mg/kg) produced changes in both conventional and ethological measures (increased percentage of open arm time and reduced risk assessment) indicative of anxiety reduction. However, these anxiolyticlike actions were less evident at higher doses. In contrast, (+)pindolol (0.1-6.4 mg/kg), metoprolol (2.0-18.0 mg/kg) and ICI 118,551 (1.0-9.0 mg/kg) were behaviourally inert under present test conditions. These data suggest that antagonist actions at 5-HT1A receptors (but not beta-adrenoceptors) are involved in the anxiolyticlike effects of (-)pindolol and pindobind 5-HT1A in the murine elevated plus-maze test.