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A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice.
Int J Neuropsychopharmacol 2010; 13(7):861-76IJ

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.

Authors+Show Affiliations

Schizophrenia Research Institute, Darlinghurst NSW, Australia. l.long@schizophreniaresearch.org.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19785914

Citation

Long, Leonora E., et al. "A Behavioural Comparison of Acute and Chronic Delta9-tetrahydrocannabinol and Cannabidiol in C57BL/6JArc Mice." The International Journal of Neuropsychopharmacology, vol. 13, no. 7, 2010, pp. 861-76.
Long LE, Chesworth R, Huang XF, et al. A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. Int J Neuropsychopharmacol. 2010;13(7):861-76.
Long, L. E., Chesworth, R., Huang, X. F., McGregor, I. S., Arnold, J. C., & Karl, T. (2010). A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. The International Journal of Neuropsychopharmacology, 13(7), pp. 861-76. doi:10.1017/S1461145709990605.
Long LE, et al. A Behavioural Comparison of Acute and Chronic Delta9-tetrahydrocannabinol and Cannabidiol in C57BL/6JArc Mice. Int J Neuropsychopharmacol. 2010;13(7):861-76. PubMed PMID: 19785914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A behavioural comparison of acute and chronic Delta9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. AU - Long,Leonora E, AU - Chesworth,Rose, AU - Huang,Xu-Feng, AU - McGregor,Iain S, AU - Arnold,Jonathon C, AU - Karl,Tim, Y1 - 2009/09/29/ PY - 2009/9/30/entrez PY - 2009/9/30/pubmed PY - 2011/1/11/medline SP - 861 EP - 76 JF - The international journal of neuropsychopharmacology JO - Int. J. Neuropsychopharmacol. VL - 13 IS - 7 N2 - 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. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/19785914/abstract/A_behavioural_comparison_of_ L2 - https://academic.oup.com/ijnp/article-lookup/doi/10.1017/S1461145709990605 DB - PRIME DP - Unbound Medicine ER -