A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.
Cannabis contains over 70 unique compounds and its abuse is linked to an increased risk of developing schizophrenia. The behavioural profiles of the psychotropic cannabis constituent Delta9-tetrahydrocannabinol (Delta9-THC) and the non-psychotomimetic constituent cannabidiol (CBD) were investigated with a battery of behavioural tests relevant to anxiety and positive, negative and cognitive symptoms of schizophrenia. Male adult C57BL/6JArc mice were given 21 daily intraperitoneal injections of vehicle, Delta9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Delta9-THC produced the classic cannabinoid CB1 receptor-mediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, Delta9-THC (10 mg/kg) produced locomotor-independent anxiogenic effects in the open-field and light-dark tests. Chronic CBD produced moderate anxiolytic-like effects in the open-field test at 50 mg/kg and in the light-dark test at a low dose (1 mg/kg). Acute and chronic Delta9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Delta9-THC (0.3, 3 and 10 mg/kg) or CBD (1, 5 and 50 mg/kg) and by chronic CBD (1 mg/kg). Chronic CBD (50 mg/kg) attenuated dexamphetamine (5 mg/kg)-induced hyperlocomotion, suggesting an antipsychotic-like action for this cannabinoid. Chronic Delta9-THC decreased locomotor activity before and after dexamphetamine administration suggesting functional antagonism of the locomotor stimulant effect. These data provide the first evidence of anxiolytic- and antipsychotic-like effects of chronic but not acute CBD in C57BL/6JArc mice, extending findings from acute studies in other inbred mouse strains and rats.
Schizophrenia Research Institute, Darlinghurst NSW, Australia. l.long@schizophreniaresearch.org.au
Leonora E
LE
Long
Rose
R
Chesworth
Xu-Feng
XF
Huang
Iain S
IS
McGregor
Jonathon C
JC
Arnold
Tim
T
Karl
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D017440:Photoperiod; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy; D012565:Schizophrenic Psychology; D055139:Sensory Gating / Q000187:drug effects; D013997:Time Factors
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D002185:Cannabidiol; D013759:Dronabinol