Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol.
A A Boucher, Jonathon C Arnold, L Duffy, P R Schofield, Jacques Micheau, Tim Karl
Psychopharmacology June 2007 DOI: 10.1007/s00213-007-0721-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Heterozygous Nrg1 transmembrane-domain knockout mice and wild-type-like mice |
| Intervention | THC |
| Dose | 0, 5, or 10 mg/kg i.p. |
| Measures | open field, hole board, light-dark, elevated plus maze, social interaction, prepulse inhibition |
| Topics | Cannabis |
| Key findings | Nrg1 heterozygous mice were more sensitive to the acute effects of THC than wild-type mice, including greater locomotor suppression and enhanced prepulse inhibition, indicating that variation in the neuregulin 1 gene alters sensitivity to cannabinoid behavioral effects. |
Abstract
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. 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. 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. 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. 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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 14
- Gone to Pot – A Review of the Association between Cannabis and Psychosis Frontiers in Psychiatry May 22, 2014
- Long-term consequences of adolescent cannabinoid exposure in adult psychopathology Frontiers in Neuroscience November 10, 2014
- Human Laboratory Studies on Cannabinoids and Psychosis. Biological Psychiatry April 1, 2016
- Should Burden of Disease Estimates Include Cannabis Use as a Risk Factor for Psychosis? PLoS Medicine September 28, 2009
- Behavioral and Pharmacokinetic Profile of Indole-Derived Synthetic Cannabinoids JWH-073 and JWH-210 as Compared to the Phytocannabinoid Δ9-THC in Rats Frontiers in Neuroscience October 23, 2018
and 9 more in the library
Cites 9
- Causal association between cannabis and psychosis: examination of the evidence The British Journal of Psychiatry January 30, 2004
- Psychiatric effects of cannabis The British Journal of Psychiatry February 1, 2001
- Psychotic symptom and cannabis relapse in recent-onset psychosis The British Journal of Psychiatry August 1, 2006
- Interactions between THC and cannabidiol in mouse models of cannabinoid activity. Psychopharmacology June 2006
- Two cases of "cannabis acute psychosis" following the administration of oral cannabis BMC Psychiatry December 1, 2005
and 4 more in the library