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

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Long, Leonora E., Chesworth, Rose, Huang, Xu-Feng, McGregor, Iain S., Arnold, Jonathon C., Karl, Tim·2010·The International Journal of Neuropsychopharmacology

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 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.

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Metadata

Authors
Long, L. E., Chesworth, R., Huang, X.-F., McGregor, I. S., Arnold, J. C., & Karl, T.
Venue
The International Journal of Neuropsychopharmacology
Published
2009-09-29
Volume
13
Issue
07
Pages
861-876
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
OpenAlex
W2041273498
Cited by
206
References
8
FWCI
6.40
Type
journal article
Language
en
Open access
bronze

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