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

Roger Guy Pertwee, Marjory Ross

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)67-71
Number of pages5
JournalNeuropharmacology
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 1991

Keywords

  • DELTA-9-TETRAHYDROCANNABINOL
  • PHYSOSTIGMINE, OXOTREMORINE
  • CHLORDIAZEPOXIDE
  • CHOLINOCEPTOR ANTAGONISTS
  • CATALEPSY
  • delta-9-tetrahydrocannabinol
  • physostigmine
  • oxotremorine
  • chlordiazepoxide
  • cholinoceptor antagonists
  • catalepsy

Cite this

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title = "Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannainol to produce marked catalepsy in mice",
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.",
keywords = "DELTA-9-TETRAHYDROCANNABINOL, PHYSOSTIGMINE, OXOTREMORINE, CHLORDIAZEPOXIDE, CHOLINOCEPTOR ANTAGONISTS, CATALEPSY, delta-9-tetrahydrocannabinol, physostigmine, oxotremorine, chlordiazepoxide, cholinoceptor antagonists, catalepsy",
author = "Pertwee, {Roger Guy} and Marjory Ross",
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T1 - Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannainol to produce marked catalepsy in mice

AU - Pertwee, Roger Guy

AU - Ross, Marjory

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N2 - 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.

AB - 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.

KW - DELTA-9-TETRAHYDROCANNABINOL

KW - PHYSOSTIGMINE, OXOTREMORINE

KW - CHLORDIAZEPOXIDE

KW - CHOLINOCEPTOR ANTAGONISTS

KW - CATALEPSY

KW - delta-9-tetrahydrocannabinol

KW - physostigmine

KW - oxotremorine

KW - chlordiazepoxide

KW - cholinoceptor antagonists

KW - catalepsy

U2 - 10.1016/0028-3908(91)90044-C

DO - 10.1016/0028-3908(91)90044-C

M3 - Article

VL - 30

SP - 67

EP - 71

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 1

ER -