title: Stereoselective antagonism by the pindolol enantiomers of 8-OH-DPAT-induced changes of sleep and wakefulness.
abstract: 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 beta-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.
authors.affiliation: Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay.
authors.forename: J M
authors.initials: JM
authors.lastname: Monti
authors.forename: H
authors.initials: H
authors.lastname: Jantos
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D013237:Stereoisomerism; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; D015784:Betaxolol