Reduced type III neuregulin 1 expression does not modulate the behavioural sensitivity of mice to acute Δ9-tetrahydrocannabinol (D9-THC).
David Lloyd, David Talmage, Cynthia Shannon Weickert, Tim Karl
Pharmacology, Biochemistry, and Behavior July 2018 DOI: 10.1016/j.pbb.2018.05.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Male mice heterozygous for type III Nrg1 (type III Nrg1+/-) and control mice |
| Intervention | Δ9-tetrahydrocannabinol (D9-THC) |
| Dose | 3 or 10 mg/kg |
| Topics | Cannabis |
| Keywords | Schizophrenia Sensorimotor gating ppi Social behaviours δ9-Tetrahydrocannabinol D9-THC |
| Key findings | Acute THC reduced locomotion and social interaction and increased anxiety. Type III Nrg1 heterozygous males showed a robust sensorimotor gating deficit and reduced social following across drug conditions, but no change in behavioural susceptibility to acute THC compared with controls. The authors suggest loss of type III Nrg1 function may not be responsible for the exaggerated THC response seen in transmembrane-domain Nrg1 heterozygous mice. |
Abstract
Mice with a mutation in the transmembrane domain of the schizophrenia risk gene, neuregulin 1 (Nrg1 TM HET), are more susceptible to the neuro-behavioural effects of Δ9-tetrahydrocannabinol (D9-THC), the principal psychoactive component in cannabis. However, NRG1 is transcriptionally complex with over 30 different isoforms, most of which carry a transmembrane domain, raising the question which NRG1 isoform(s) may contribute to this phenotype. Type III NRG1/Nrg1 is the most brain abundant isoform and brain studies have identified increased levels of type III NRG1 mRNA in humans carrying a NRG1 risk haplotype for schizophrenia. To investigate whether mice heterozygous for type III Nrg1 (i.e. knockout: type III Nrg1+/-) are more susceptible to the behavioural effects of acute doses of D9-THC, we injected male mice with either vehicle or D9-THC (3 or 10 mg/kg) before testing them for locomotion, anxiety, social interaction, and sensorimotor gating. Acute D9-THC led to reduced locomotion and reduced social interaction, but increased anxiety in mice. Furthermore, type III Nrg1 males displayed a robust deficit in sensorimotor gating and demonstrated reduced following during social interaction across drug conditions. However, they did not show a change in behavioural susceptibility to acute D9-THC compared to controls. These results reinforce the validity of type III Nrg1+/- mice for schizophrenia research and suggest that loss of function of type III Nrg1 may not be responsible for the exaggerated response to acute D9-THC observed in heterozygous Nrg1 TM mice. This highlights the importance of careful consideration of Nrg1 isoform type differences.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 1
Cites 7
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