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01-01 Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of D9-tetrahydrocannabinol

Published online by Cambridge University Press:  24 June 2014

JC Arnold ,
AA Boucher ,
L Duffy ,
PR Schofield ,
J Micheau  and
TF Karl
JC Arnold
Affiliation:
Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), New South Wales, Australia
AA Boucher
Affiliation:
Department of Pharmacology, University of Sydney, Sydney, New South Wales, Australia Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), New South Wales, Australia Laboratoire de Neurosciences Cognitives, Université Bordeaux I, Talence, France
L Duffy
Affiliation:
Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), New South Wales, Australia Neuroscience Research Program, Garvan Institute of Medical Research, New South Wales, Australia
PR Schofield
Affiliation:
Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), New South Wales, Australia Neuroscience Research Program, Garvan Institute of Medical Research, New South Wales, Australia Prince of Wales Medical Research Institute, Sydney, New South Wales, Australia University of New South Wales, Sydney, New South Wales, Australia
J Micheau
Affiliation:
Laboratoire de Neurosciences Cognitives, Université Bordeaux I, Talence, France
TF Karl
Affiliation:
Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), New South Wales, Australia Neuroscience Research Program, Garvan Institute of Medical Research, New South Wales, Australia
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Abstract

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Type
Abstracts from ‘Brainwaves’— The Australasian Society for Psychiatric Research Annual Meeting 2006, 6–8 December, Sydney, Australia
Information
Acta Neuropsychiatrica , Volume 18 , Issue 6 , December 2006 , pp. 313
Copyright
Copyright © 2006 Blackwell Munksgaard

Rationale:

Environmental stressors such as cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to the disease. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. Aim: The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of 9-tetrahydrocannabinol (THC), the major psychotropic component of cannabis.

Methods:

Heterozygous Nrg1 transmembrane-domain knockout mice (Nrg1 HET) were treated with acute THC (0, 5 or 10 mg/kg i.p.) 30 min before being tested in the open field (OF), hole board, light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests.

Results:

Nrg1 HET mice showed differences in baseline behaviour in regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared with wild-type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in per cent PPI than WT mice. The effects of THC on anxiety-related behaviour were task dependent, with Nrg1 HET mice being more susceptible than WT mice to the anxiogenic effects of THC in LD, but not in the EPM, SI and OF tests.

Conclusions:

Nrg1 HET mice were more sensitive to the acute effects of THC in an array of different behaviours including those that model symptoms of schizophrenia. It appears that variation in the schizophrenia-related neuregulin 1 gene alters the sensitivity to the behavioural effects of cannabinoids.