Drugs which stimulate or facilitate central GABAergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice.
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.
Pertwee
R G
RG
Department of Pharmacology, University of Aberdeen, Scotland.
Greentree
S G
SG
Swift
P A
PA
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002375:Catalepsy / Q000503:physiopathology*; D013759:Dronabinol / Q000494:pharmacology*; D004357:Drug Synergism; D005442:Flumazenil / Q000494:pharmacology; D005475:Flupenthixol / Q000494:pharmacology; D005479:Flurazepam / Q000494:pharmacology; D018756:GABA Antagonists; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects; D013331:Strychnine / Q000494:pharmacology; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018756:GABA Antagonists; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; D000625:Aminooxyacetic Acid; D013654:Taurine; D009118:Muscimol; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; C001355:tramiprosate; D013759:Dronabinol; D005475:Flupenthixol; D001418:Baclofen; D013331:Strychnine; D005479:Flurazepam; D001640:Bicuculline; D000078308:Tiagabine