An investigation of the involvement of GABA in certain pharmacological effects of delta-9-tetrahydrocannabinol.
Experiments were performed with mice to determine whether doses of the benzodiazepine, flurazepam, or the GABA uptake inhibitor, NO-328, known to potentiate catalepsy induced by delta-9-tetrahydrocannabinol (THC), would also interact synergistically with THC in the production of certain other effects. No synergism was detected either in the production of antinociception (tail flick test) or in a test in which the ability of flurazepam to delay onset of clonic convulsions induced by intravenous infusion of pentylenetetrazole was compared in the presence and absence of THC or cannabidiol. The hypothermic effect of THC was unaffected by NO-328 but enhanced by flurazepam, albeit only at doses higher than those needed to potentiate THC-induced catalepsy. In vitro experiments with guinea pig ileum showed that the ability of THC to inhibit electrically evoked contractions was unaffected by delta-amino-n-valeric acid, a GABA(B) receptor antagonist, and that preparations rendered tolerant to GABA responded normally to THC. Contractions induced by GABA in unstimulated ileal longitudinal muscle were attenuated by THC. We conclude that there is little evidence from our data that any of the THC effects studied were GABA mediated.
Pertwee
R G
RG
Division of Pharmacology, School of Biomedical Sciences, Marischal College University of Aberdeen, Scotland.
Browne
S E
SE
Ross
T M
TM
Stretton
C D
CD
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002185:Cannabidiol / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D004558:Electric Stimulation; D005479:Flurazepam / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009557:Nipecotic Acids / Q000494:pharmacology; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000596:Amino Acids; D021542:Amino Acids, Neutral; D000700:Analgesics; D000927:Anticonvulsants; D009557:Nipecotic Acids; D002185:Cannabidiol; D005680:gamma-Aminobutyric Acid; C013809:5-aminovaleric acid; D013759:Dronabinol; D005479:Flurazepam; D010433:Pentylenetetrazole; D000078308:Tiagabine