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

Article date: 1988/12/1

PubMed ID: 2854226

Journal name: Neuropharmacology (ISSN: 0028-3908)


In experiments in which mice were placed with their forelegs over a 4 cm high horizontal bar, pretreatment with delta-9-tetrahydrocannabinol (THC; 10 mg/kg i.p.) significantly delayed descent from the bar. This response to THC was markedly enhanced by doses of amino-oxyacetic acid, flurazepam, cis(Z)-flupentixol, muscimol, (-)-baclofen and NO-328 having little or no effect when given alone. No synergism was detected between THC and (+)-baclofen or trans(E)-flupentixol. The interactions between THC and flurazepam, amino-oxyacetic acid and NO-328 were attenuated by (+)-bicuculline and by homotaurine, but not by strychnine. The interaction between THC and (-)-baclofen was prevented by homotaurine but not by (+)-bicuculline whereas only (+)-bicuculline reduced the interactions of THC with muscimol and cis(Z)-flupentixol. Flumazenil prevented the interaction between THC and flurazepam but not that between THC and NO-328. The results suggest that the synergistic interactions observed in this study depended on the activation of GABAA and/or GABAB receptors, probably located in extrapyramidal GABAergic pathways.

This document is available from: http://directlinks.cc/files/muscimol/2854226.pdf

Author List: Pertwee R G, Greentree S G, Swift P A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: GABA Antagonists; Nipecotic Acids; Receptors, GABA-A; Aminooxyacetic Acid; Taurine; Muscimol; Flumazenil; gamma-Aminobutyric Acid; tramiprosate; Dronabinol; Flupenthixol; Baclofen; Strychnine; Flurazepam; Bicuculline; tiagabine;

Mesh terms: Aminooxyacetic Acid/pharmacology; Animals; Baclofen/pharmacology; Bicuculline/pharmacology; Catalepsy/physiopathology; Dronabinol/pharmacology; Drug Synergism; Flumazenil/pharmacology; Flupenthixol/pharmacology; Flurazepam/pharmacology; GABA Antagonists; Male; Mice; Muscimol/pharmacology; Nipecotic Acids/pharmacology; Receptors, GABA-A/drug effects; Strychnine/pharmacology; Taurine/analogs & derivatives; gamma-Aminobutyric Acid/metabolism;

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