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 m g/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-dihydroxytry ptamine (5,7-DHT)-injected rats. 5,7-DHT-treated animals showed a mark ed and significant serotonin and 5-HIAA depletion in the raphe regions of the pens and upper brain stem, cerebral cortex, hippocampus, and s triatum. Subcutaneous administration of the partial agonists to both t he vehicle-infused and the 5,7-DHT-treated animals significantly incre ased waking (W) and reduced light sleep (LS), slow-wave sleep (SWS), a nd REM sleep (REMS). Pretreatment with (-)-pindolol (2.0 mg/kg) revers ed 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, ips apirone, or gepirone depends upon the activation of postsynaptic 5-HT, , receptors. The well-known anxiolytic action observed after chronic a dministration of the azapirones seems to be related to mechanisms othe r that these involved in their stimulant effect.