Sleep effects following intrathecal administration of the 5-HT1A agonist 8-OH-DPAT and the NMDA antagonist AP-5 in rats

Brain Res. 1995 Sep 18;692(1-2):251-8. doi: 10.1016/0006-8993(95)00689-n.

Abstract

The modulating effect of an intrathecally (i.t.) administered 5-HT1A agonist and an NMDA antagonist on sleep, waking and EEG power spectra was investigated in rats. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (38 nmol) increased total slow wave sleep (TSWS) and decreased waking over the 8 h recording period. The TSWS increase was mostly due to an increase in SWS1. Sleep latency to SWS1 was also reduced. The NMDA antagonist dl-2-amino 5-phosphonovaleric acid (AP-5) (31.5 nmol) reduced waking. SWS1 was increased, but TSWS was not changed. An increase in REM sleep was seen during the last part of the recording. Combined treatment with 8-OH-DPAT and AP-5 reduced waking and increased TSWS. No change in REM sleep was seen. There were no systematic changes in either waking, TSWS or REM fronto-frontal or fronto-parietal EEG power spectrum after any of the treatments. The results suggest that in the spinal cord stimulation of 5-HT1A receptors have a dampening effect on transmission of sensory information, leading to deactivation and thereby increased possibilities for sleep induction. Blockade of the NMDA receptors may also lead to a small dampening of sensory transmission with similar consequences.

MeSH terms

  • 2-Amino-5-phosphonovalerate / administration & dosage
  • 2-Amino-5-phosphonovalerate / pharmacology*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / administration & dosage
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Drug Interactions
  • Electroencephalography / drug effects
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Injections, Spinal
  • Male
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology*
  • Sleep / drug effects*
  • Sleep, REM / drug effects
  • Wakefulness / physiology

Substances

  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Serotonin Receptor Agonists
  • 2-Amino-5-phosphonovalerate
  • 8-Hydroxy-2-(di-n-propylamino)tetralin