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Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol.
Psychopharmacology (Berl). 2007 Jun; 192(3):325-36.P

Abstract

RATIONALE

Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia.

OBJECTIVES

The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Delta(9)-tetrahydrocannabinol (THC), the major psychotropic component of cannabis.

MATERIALS AND 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 using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests.

RESULTS

Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % 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.

Authors+Show Affiliations

Boucher AA
Neuroscience Institute of Schizophrenia and Allied Disorders, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia.
Arnold JC
No affiliation info available
Duffy L
No affiliation info available
Schofield PR
No affiliation info available
Micheau J
No affiliation info available
Karl T
No affiliation info available

MeSH

AnimalsAnxietyBehavior, AnimalDose-Response Relationship, DrugDronabinolExploratory BehaviorGenotypeHallucinogensMaleMiceMice, KnockoutMotor ActivityNeuregulin-1Psychotropic DrugsReflex, StartleSchizophreniaSocial Behavior

Pub Type(s)

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

Language

eng

PubMed ID

17333138

Citation

Boucher, A A., et al. "Heterozygous Neuregulin 1 Mice Are More Sensitive to the Behavioural Effects of Delta9-tetrahydrocannabinol." Psychopharmacology, vol. 192, no. 3, 2007, pp. 325-36.
Boucher AA, Arnold JC, Duffy L, et al. Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol. Psychopharmacology (Berl). 2007;192(3):325-36.
Boucher, A. A., Arnold, J. C., Duffy, L., Schofield, P. R., Micheau, J., & Karl, T. (2007). Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol. Psychopharmacology, 192(3), 325-36.
Boucher AA, et al. Heterozygous Neuregulin 1 Mice Are More Sensitive to the Behavioural Effects of Delta9-tetrahydrocannabinol. Psychopharmacology (Berl). 2007;192(3):325-36. PubMed PMID: 17333138.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol. AU - Boucher,A A, AU - Arnold,J C, AU - Duffy,L, AU - Schofield,P R, AU - Micheau,J, AU - Karl,T, Y1 - 2007/02/28/ PY - 2006/07/13/received PY - 2007/01/22/accepted PY - 2007/3/3/pubmed PY - 2007/8/10/medline PY - 2007/3/3/entrez SP - 325 EP - 36 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 192 IS - 3 N2 - RATIONALE: Cannabis use may precipitate schizophrenia especially if the individual has a genetic vulnerability to this mental disorder. Human and animal research indicates that neuregulin 1 (Nrg1) is a susceptibility gene for schizophrenia. OBJECTIVES: The aim of this study was to investigate whether dysfunction in the Nrg1 gene modulates the behavioural effects of Delta(9)-tetrahydrocannabinol (THC), the major psychotropic component of cannabis. MATERIALS AND 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 using open field (OF), hole board (HB), light-dark (LD), elevated plus maze (EPM), social interaction (SI) and prepulse inhibition (PPI) tests. RESULTS: Nrg1 HET mice showed differences in baseline behaviour with regard to locomotor activity, exploration and anxiety. More importantly, they were more sensitive to the locomotor suppressant actions of THC compared to wild type-like (WT) mice. In addition, Nrg1 HET mice expressed a greater THC-induced enhancement in % 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/17333138/Heterozygous_neuregulin_1_mice_are_more_sensitive_to_the_behavioural_effects_of_Delta9_tetrahydrocannabinol_ DB - PRIME DP - Unbound Medicine ER -