Sleep/waking effects following intrathecal administration of the 5-HT(1A) Agonist 8-OH-DPAT alone and in combination with the putative 5-HT(1A) antagonist NAN-190 in rats.
Sleep, waking, and EEG power spectra were investigated in rats after intrathecal (IT) administration of a 5-HT(1A) agonist and a 5-HT(1A) antagonist. Total slow wave sleep (TSWS) was increased and waking was decreased over the 8-h recording period after the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol). Within TSWS, SWS1 was unchanged while SWS-2 tended to be increased. The 5-HT(1A) antagonist 1-[2-Methoxyphenyl)-4-(4-(2-phthalimido)-butyl]piperazine hydrobromide (NAN-190) did not change any sleep/waking stages. Combined treatment with 8-OH-DPAT and NAN-190 increased variance. Following the combination, sleep and waking were not significantly different from control. SWS-2 tended to be reduced compared to the effect of 8-OH-DPAT alone. There were no systematic changes in neither waking nor TSWS fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments, indicating that sleep quality was not changed. The results confirm earlier data suggesting that in the spinal cord, stimulation of 5-HT(1A) receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased sleep tendency. The reason why the 8-OH-DPAT effect was not clearly antagonized by the putative 5-HT1A antagonist NAN-190, may be due to the generally weak antagonistic and also partial agonistic effect of NAN-190 as reported in the literature.
Bjørkum
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Department of Physiology, University of Bergen, Norway.
Ursin
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin