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A behavioural comparison of acute and chronic ∆9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice

Journal Article


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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 D9-tetrahydrocannabinol

    (D9-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, D9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). D9-THC produced the classic cannabinoid CB1 receptormediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, D9-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 D9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with D9-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 D9-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


  •   Long, Leonora E. (external author)
  •   Chesworth, Rose (external author)
  •   Huang, Xu-Feng
  •   McGregor, Ian (external author)
  •   Dr Jonathon Arnold, Jonathon (external author)
  •   Karl, Tim (external author)

Publication Date


  • 2010

Citation


  • Long, L. E., Chesworth, R., Huang, X., McGregor, I., Arnold, J. & Karl, T. (2010). A behavioural comparison of acute and chronic ∆9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. International Journal of Neuropsychopharmacology, 13 (7), 861-876.

Scopus Eid


  • 2-s2.0-77957228353

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3247&context=hbspapers

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/2194

Has Global Citation Frequency


Number Of Pages


  • 15

Start Page


  • 861

End Page


  • 876

Volume


  • 13

Issue


  • 7

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 D9-tetrahydrocannabinol

    (D9-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, D9-THC (0.3, 1, 3 or 10 mg/kg) or CBD (1, 5, 10 or 50 mg/kg). D9-THC produced the classic cannabinoid CB1 receptormediated tetrad of hypolocomotion, analgesia, catalepsy and hypothermia while CBD had modest hyperthermic effects. While sedative at this dose, D9-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 D9-THC (10 mg/kg) decreased the startle response while CBD had no effect. Prepulse inhibition was increased by acute treatment with D9-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 D9-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


  •   Long, Leonora E. (external author)
  •   Chesworth, Rose (external author)
  •   Huang, Xu-Feng
  •   McGregor, Ian (external author)
  •   Dr Jonathon Arnold, Jonathon (external author)
  •   Karl, Tim (external author)

Publication Date


  • 2010

Citation


  • Long, L. E., Chesworth, R., Huang, X., McGregor, I., Arnold, J. & Karl, T. (2010). A behavioural comparison of acute and chronic ∆9-tetrahydrocannabinol and cannabidiol in C57BL/6JArc mice. International Journal of Neuropsychopharmacology, 13 (7), 861-876.

Scopus Eid


  • 2-s2.0-77957228353

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3247&context=hbspapers

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/2194

Has Global Citation Frequency


Number Of Pages


  • 15

Start Page


  • 861

End Page


  • 876

Volume


  • 13

Issue


  • 7