Evidence map›Paper›PMID 42067687›Full record

ArticlePsychopharmacology2026

Genetic risk for schizophrenia modulates WIN 55,212-2 reward: Evidence from a heterozygous transmembrane domain neuregulin 1 mutant mouse model.

Rose Chesworth, Georgia Watt, Jaime Howard, Georgina Ding, Tim Karl

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Article in Psychopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Rose ChesworthSchool of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia.
Georgia WattCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Jaime HowardSchool of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia.
Georgina DingSchool of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia.
Tim KarlSchool of Medicine, Western Sydney University, Campbelltown, NSW, 2560, Australia. t.karl@westernsydney.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCannabis abuse rates are up to ten times higher in individuals with schizophrenia than the general population, but it is unclear what is driving this high level of comorbidity. Genetic predisposition for schizophrenia may increase the risk of cannabis abuse; however, there is limited empirical support for this.

methodsWe investigated this question using a well-established genetic mouse model of schizophrenia risk, the heterozygous transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mouse, which also shows behavioural and neural susceptibility to cannabis components. WIN 55,212-2 (WIN), a cannabinoid 1 (CB1) receptor agonist, was used to model the rewarding and aversive properties of cannabis. We first validated a conditioned place preference protocol to determine rewarding and aversive doses of WIN administration in C57BL/6J mice, the background strain of our schizophrenia mouse model. We then investigated the effects of these WIN dose regimes on place preference and locomotion in male and female Nrg1 TM HET mice and their control wildtype-like littermates.

resultsWe found that low dose WIN (0.1 mg/kg) was rewarding in wildtype-like, but not in Nrg1 TM HET mice of both sexes. Conversely, male and female mice of both genotypes found high dose WIN (3 mg/kg) aversive. While all mice showed a similar locomotor response to low dose WIN administration, male Nrg1 TM HET mice showed an earlier development of locomotor tolerance to high dose WIN, with no differences in WIN-induced locomotor sedation in female mice.

conclusionOur findings suggest that genetic risk for schizophrenia can modulate the rewarding properties of the CB1 receptor agonist WIN and support the hypothesis that comorbidity between schizophrenia and cannabis use disorder may in part be driven by shared genetic risk factors.

Indexed as

CannabinoidCannabisLocomotor sensitizationMouse modelPlace preference

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.