Depletion of brain serotonin by 5,7-DHT: effects on the 8-OH-DPAT-induced changes of sleep and waking in the rat

Psychopharmacology (Berl). 1994 Jun;115(1-2):273-7. doi: 10.1007/BF02244783.

Abstract

The effect of 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness was studied in rats with selective serotonin depletion after ICV administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Injection of 8-OH-DPAT to vehicle-treated animals induced biphasic effects, such that low doses (0.010 mg/kg) which act perferentially on the somatodendritic autoreceptor decreased wakefulness (W) and increased slow wave sleep (SWS), while higher doses (0.375 mg/kg) which stimulate postsynaptic receptors caused opposite effects. REM sleep was suppressed irrespective of the dosage given. Injection of the 0.010 mg/kg dose in the 5,7-DHT-treated rats did not result in significant changes in sleep or W. On the other hand, the 0.375 mg/kg dose produced changes in sleep variables which were similar to those described in the vehicle-treated animals. Our findings tend to indicate that increased SWS after low doses of 8-OH-DPAT depends upon the activation of inhibitory somatodendritic 5-HT1A receptors, while increased W after higher doses of the compound is related to stimulation of postsynaptic receptors.

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology*
  • Animals
  • Biogenic Monoamines / metabolism
  • Brain Chemistry / drug effects*
  • Dose-Response Relationship, Drug
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, Presynaptic / drug effects
  • Receptors, Serotonin / drug effects
  • Serotonin / metabolism*
  • Serotonin / physiology
  • Sleep / drug effects*
  • Sleep, REM / drug effects
  • Wakefulness / drug effects*

Substances

  • Biogenic Monoamines
  • Receptors, Presynaptic
  • Receptors, Serotonin
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Hydroxyindoleacetic Acid
  • 8-Hydroxy-2-(di-n-propylamino)tetralin