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  • Title: Drugs which stimulate or facilitate central GABAergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice.
    Author: Pertwee RG, Greentree SG, Swift PA.
    Journal: Neuropharmacology; 1988 Dec; 27(12):1265-70. PubMed ID: 2854226.
    Abstract:
    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.
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