A behavioural comparison of acute and chronic Δ9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice

Authors

Ian McGregor, University of Sydney
Xu-Feng Huang, University of WollongongFollow
Tim Karl, The University of New South Wales
Jonathon Arnold, Univeristy of Sydney
Rose Chesworth, Schizophrenia Research Institute, Darlinghurst
Leonora E. Long, Schizophrenia Research Institute, Darlinghurst

RIS ID

32950

Publication Details

Long, L. E., Chesworth, R., Huang, X., McGregor, I., Arnold, J. & Karl, T. (2010). A behavioural comparison of acute and chronic Δ9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. International Journal of Neuropsychopharmacology, 13 (7), 861-876.

Abstract

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 Δ⁹-tetrahydrocannabinol (Δ⁹-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, Δ⁹-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). Δ⁹-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, Δ⁹-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 Δ⁹-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with Δ⁹-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 Δ⁹-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.