STEREOSELECTIVE ANTAGONISM BY THE PINDOLOL ENANTIOMERS OF 8-OH-DPAT-INDUCED CHANGES OF SLEEP AND WAKEFULNESS

The effects of 5-HT1A receptor agonist 8-OH-DPAT were compared with those of the mixed beta-adrenoceptor and 5-HT1A receptor antagonist (-)pindolol, and the selective B-adrenoceptor antagonist betaxolol in rats implanted for chronic sleep recordings, 8-OH-DPAT (0.375 mg/kg) significantly increased wakefulness and decreased slow wave sleep (SWS) and REM sleep (REMS). At 2.0-4.0 mg/kg (-)pindolol reduced REMS. Betaxolol in doses of 1.0 and 2.0 mg/kg did not significantly modify sleep variables. Pretreatment with (-)pindolol (2.0-4.0 mg/kg) reversed the effect of 8-OH-DPAT on waking and SWS, while (+)pindolol (4.0 mg/kg) and betaxolol (2.0 mg/kg) were ineffective in this respect. The stereoselective antagonism by the pindolol enantiomers supports the proposal that 8-OH-DPAT-induced increase of waking and decrease of SWS depends on the activation of 5-HT1A receptors. The absence of antagonism by betaxolol tends to indicate that prevention by (-)pindolol of waking increase did not involve beta-adrenoceptors.