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

Brain Res Bull. 1996;39(6):373-9. doi: 10.1016/0361-9230(96)00029-9.

Abstract

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.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Analysis of Variance
  • Animals
  • Electroencephalography / drug effects
  • Injections, Spinal
  • Male
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Serotonin Antagonists / pharmacology*
  • Serotonin Receptor Agonists / pharmacology*
  • Sleep / drug effects*
  • Wakefulness / drug effects*

Substances

  • Piperazines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin