Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice.
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.
Pertwee
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RG
Division of Pharmacology, Marischal College, University of Aberdeen, U.K.
Ross
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TM
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D013759:Dronabinol / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009388:Neostigmine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D001286:Atropine Derivatives; D010277:Parasympathomimetics; D009388:Neostigmine; D010095:Oxotremorine; D001285:Atropine; D013759:Dronabinol; C006649:methylatropine; D010830:Physostigmine; D012601:Scopolamine; D000109:Acetylcholine