INFLUENCE OF 5-HT1A RECEPTOR ANTAGONISM ON PLUS-MAZE BEHAVIOR IN MICE.1. PINDOLOL ENANTIOMERS AND PINDOBIND 5-HT1A

Studies on the behavioural effects of 5-hydroxytryptamine receptor sub type 1A (5-HT1A) antagonists may provide important clues to the precis e role of 5-HT1A receptor mechanisms in anxiety. In the first of a ser ies of experiments designed to address this issue, the effects of mixe d 5-HT1A and beta-adrenergic receptor antagonists pindolol enantiomers and pindobind 5-HT1A and of metoprolol and ICI 118,551 (selective bet a(1)- and beta(2)-adrenoceptor antagonists, respectively) were assesse d in the mouse elevated plus-maze using ethological techniques. Result s showed that, at lower doses, (-)pindolol (0.1-1.6 mg/kg) and pindobi nd 5-HT1A (0.1-0.5 mg/kg) produced changes in both conventional and et hological measures (increased percentage of open arm time and reduced risk assessment) indicative of anxiety reduction. However, these anxio lyticlike actions were less evident at higher doses. In contrast, (+)p indolol (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 n ot beta-adrenoceptors) are involved in the anxiolyticlike effects of ( -)pindolol and pindobind 5-HT1A in the murine elevated plus-maze test. (C) 1997 Elsevier Science Inc.