Biphasic effect of chlorpromazine on rat paradoxical sleep: a study of dose-related mechanisms

Eur J Pharmacol. 1978 Jun 1;49(3):251-7. doi: 10.1016/0014-2999(78)90100-0.

Abstract

The experiments reported here investigated the effect of chlorpromazine (CPZ) alone or after inhibition of catecholamine (CA) synthesis on paradoxical sleep (PS) in the rat. The dose--response curve for CPZ was biphasic with enhancement of PS after low doses, and depression of PS after higher doses. In contrast, low doses of CPZ after inhibition of CA synthesis markedly decreased PS. This decrease was greater after tyrosine hydroxylase inhibition than after dopamine-beta-hydroxylase inhibition. These results support the view that low doses of CPZ produce increased activity in brain CA synapses, and that both dopamine and noradrenaline participate in the control of PS in the rat.

MeSH terms

  • Animals
  • Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / pharmacology
  • Chlorpromazine / pharmacology*
  • Dopamine beta-Hydroxylase / antagonists & inhibitors
  • Dose-Response Relationship, Drug
  • Male
  • Methyltyrosines / pharmacology
  • Rats
  • Sleep Stages / drug effects
  • Sleep, REM / drug effects*
  • Tyrosine 3-Monooxygenase / antagonists & inhibitors

Substances

  • Methyltyrosines
  • Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide
  • Tyrosine 3-Monooxygenase
  • Dopamine beta-Hydroxylase
  • Chlorpromazine