Sleep and waking in 5,7-DHT-lesioned or (-)-pindolol-pretreated rats after administration of buspirone, ipsapirone, or gepirone.
The effects of partial 5-HT1A receptor agonists buspirone (0.010-4.0 mg/kg), ipsapirone (0.010-6.0 mg/kg), and gepirone (0.025-4.0 mg/kg) on sleep and waking were studied in vehicle-treated and 5,7-dihydroxytryptamine (5,7-DHT)-injected rats. 5,7-DHT-treated animals showed a marked and significant serotonin and 5-HIAA depletion in the raphe regions of the pons and upper brain stem, cerebral cortex, hippocampus, and striatum. Subcutaneous administration of the partial agonists to both the vehicle-infused and the 5,7-DHT-treated animals significantly increased waking (W) and reduced light sleep (LS), slow-wave sleep (SWS), and REM sleep (REMS). Pretreatment with (-)pindolol (2.0 mg/kg) reversed the effects of buspirone and gepirone on W and non-REM sleep (LS + SWS) whereas REMS remained suppressed. (-)-Pindolol failed to reverse the effects of ipsapirone on sleep and W. The present results tend to indicate that increased W after acute administration of buspirone, ipsapirone, or gepirone depends upon the activation of postsynaptic 5-HT1A receptors. The well-known anxiolytic action observed after chronic administration of the azapirones seems to be related to mechanisms other that these involved in their stimulant effect.
Monti
J M
JM
Department of Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montevideo, Uruguay.
Jantos
H
H
Silveira
R
R
Reyes-Parada
M
M
Scorza
C
C
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010869:Pindolol / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018490:Serotonin Agents / Q000633:toxicity*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D015306:Biogenic Monoamines; D011743:Pyrimidines; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D015116:5,7-Dihydroxytryptamine; C043077:ipsapirone; D010869:Pindolol; C039979:gepirone; D002065:Buspirone