Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice

Neuropharmacology. 1991 Jan;30(1):67-71. doi: 10.1016/0028-3908(91)90044-c.

Abstract

In experiments in which mice were placed with their forepaws over a 4 cm high horizontal bar, delta-9-tetrahydrocannabinol (THC; 10 mg/kg i.p.) delayed descent from the bar. This effect on descent latency was markedly enhanced by physostigmine (0.05 or 0.25 mg/kg s.c.) and oxotremorine (0.04 or 0.08 mg/kg s.c.), administered immediately before THC. These interactions were attenuated by atropine (2.0 mg/kg s.c.) and (-)-scopolamine (1.9 mg/kg s.c.) but not by atropine methyl nitrate (2.11 mg/kg s.c.), which does not readily cross the blood-brain barrier. However, atropine methyl nitrate did prevent salivation induced by oxotremorine in the presence of THC. No synergism was detected between THC and neostigmine (0.047 mg/kg s.c.). Atropine and (-)-scopolamine also decreased the ability of chlordiazepoxide (10 mg/kg s.c.) to enhance the effect of THC on descent latency. The interaction was not antagonized by atropine methyl nitrate or mecamylamine (1.17 or 2.34 mg/kg s.c.). These results point to an involvement of central acetylcholine-releasing pathways in the cataleptic response of mice to THC.

MeSH terms

  • Acetylcholine / physiology*
  • Animals
  • Atropine / pharmacology
  • Atropine Derivatives / pharmacology
  • Body Temperature / drug effects
  • Catalepsy / chemically induced
  • Catalepsy / physiopathology*
  • Dronabinol / pharmacology*
  • Drug Synergism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neostigmine / pharmacology
  • Oxotremorine / pharmacology
  • Parasympathomimetics / pharmacology*
  • Physostigmine / pharmacology
  • Scopolamine / pharmacology
  • Synaptic Transmission / drug effects*

Substances

  • Atropine Derivatives
  • Parasympathomimetics
  • Neostigmine
  • Oxotremorine
  • Atropine
  • Dronabinol
  • methylatropine
  • Physostigmine
  • Scopolamine
  • Acetylcholine