Systemic administration and local microinjection into the central nervous system of the 5-HT(7) receptor agonist LP-211 modify the sleep-wake cycle in the rat

Behav Brain Res. 2014 Feb 1:259:321-9. doi: 10.1016/j.bbr.2013.11.030. Epub 2013 Nov 25.

Abstract

The effects of LP-211, a selective serotonin 5-HT7 receptor agonist were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of LP-211 (2.5-10mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced rapid-eye-movement sleep (REMS) and the number of REM periods during the 6-h recording period. Direct infusion of LP-211 into the dorsal raphe nucleus (DRN) (2-6 mM), locus coeruleus nucleus (LC) (4 mM), basal forebrain (horizontal limb of the diagonal band of Broca) (HDB) (2 mM) or laterodorsal tegmental nucleus (LDT) (4 mM) induced also a decrease of REMS. Additionally, microinjection of the 5-HT7 receptor ligand into the HDB (2 mM) augmented W. Presently, there is no satisfactory explanation for the effect of 5-HT7 receptor activation on W and REMS occurrence. Additional studies are required to characterize the neurotransmitter systems responsible for the actions of LP-211 on the behavioral states.

Keywords: 5-HT; 5-HT(7) receptor; BFB; Basal forebrain; CNS; DRN; Dorsal raphe nucleus; EEG; EMG; GABA; HDB; LC; LDT; LDT/PPT; LP-211; LS; Locus coeruleus nucleus; PRF; REMS; SCN; SWS; Serotonin; W; basal forebrain; central nervous system; dorsal raphe nucleus; electroencephalogram; electromyogram; horizontal limb of the diagonal band of Broca; laterodorsal and pedunculopontine tegmental nuclei; laterodorsal tegmental nucleus; light sleep; locus coeruleus nucleus; pontine reticular formation; rapid-eye-movement sleep; serotonin; slow wave sleep; suprachiasmatic nucleus; wakefulness; γ-aminobutyric acid.

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Circadian Rhythm / drug effects*
  • Dose-Response Relationship, Drug
  • Electroencephalography
  • Electromyography
  • Male
  • Microinjections
  • Piperazines / pharmacology*
  • Rats
  • Rats, Wistar
  • Serotonin Receptor Agonists / pharmacology*
  • Sleep / drug effects
  • Time Factors
  • Wakefulness / drug effects

Substances

  • N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide
  • Piperazines
  • Serotonin Receptor Agonists