Delta-9-tetrahydrocannabinol-induced catalepsy in mice is enhanced by pretreatment with flurazepam or chlordiazepoxide.
Pretreatment with flurazepam (3 mg/kg s.c.) or chlordiazepoxide (5.5-30 mg/kg s.c.) at an ambient temperature of 34 degrees C, markedly enhanced the cataleptic response of mice to delta-9-tetrahydrocannabinol (THC; 5-20 mg/kg i.p.) as measured in a bar test. Also, the incidence of loss of the righting response was significantly greater in mice receiving a subhypnotic dose of flurazepam (0.3-3 mg/kg s.c.), followed by THC (5-20 mg/kg i.p.), than in animals receiving THC preceded by saline. Loss of the righting response was not associated with any gross reduction in skeletal muscle tone (inclined screen and wire grip tests) and it was proposed that the animals were not anaesthetized but instead could be placed on their backs because flurazepam had enhanced the cataleptic effect of THC. Loss of the righting response produced in mice by pentobarbitone (60 mg/kg i.p.) or by a large dose of flurazepam (300 mg/kg s.c.) was associated with a marked loss of muscle tone and probably indicated the induction of anaesthesia. It is possible that THC interacts with benzodiazepines by increasing synaptic concentrations of gamma-aminobutyric acid (GABA). However, many other possible mechanisms exist and these cannot yet be excluded.
Pertwee
R G
RG
Department of Pharmacology, University of Aberdeen, Marischal College, Scotland.
Greentree
S G
SG
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D013759:Dronabinol / Q000633:toxicity*; D004357:Drug Synergism; D005479:Flurazepam / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013997:Time Factors
D002707:Chlordiazepoxide; D013759:Dronabinol; D005479:Flurazepam