Overexpressing CNRIP1, a protein that regulates the CB1 cannabinoid receptor, in the ventral hippocampus of rats produced behavioral and neurological changes resembling schizophrenia.
Neuroscience researchers and anyone interested in the biological mechanisms linking the cannabinoid system to psychosis.
CNRIP1 overexpression alone was sufficient to produce psychosis-like changes
What the researchers found
Viral-mediated overexpression of CNRIP1 in the ventral hippocampus caused impairments in latent inhibition and social interaction (behavioral correlates of schizophrenia) and increased dopamine neuron population activity in the ventral tegmental area, a putative marker of psychosis.
Why it matters
Previous studies found abnormal CNRIP1 DNA methylation in postmortem brains of people with schizophrenia. This study shows that simply overexpressing this cannabinoid-regulating protein is enough to produce schizophrenia-like changes in rats.
The numbers in context
CNRIP1 overexpression impaired latent inhibition and social interaction. VTA dopamine neuron population activity was significantly increased.
How the study worked
Sprague Dawley rats received viral-mediated CNRIP1 overexpression in the ventral hippocampus. They were tested for latent inhibition, social interaction, and VTA dopamine neuron activity via electrophysiology.
What this study cannot tell us
Animal model; behavioral correlates in rats are imperfect proxies for human schizophrenia symptoms. Only one brain region (ventral hippocampus) was targeted.
How to read the evidence
Preliminary: single animal study using viral overexpression in one brain region.
When this study was published
Published in 2019.
The bigger picture
This adds a new piece to the cannabis-psychosis puzzle. Rather than focusing on THC or the CB1 receptor itself, this research points to a regulatory protein in the cannabinoid system as a potential contributor to schizophrenia pathology.
Questions still open
- Do people with schizophrenia have elevated CNRIP1 levels in the hippocampus? Could CNRIP1 serve as a biomarker or drug target for psychosis? Does adolescent cannabis use alter CNRIP1 expression?
Common questions
What is CNRIP1?
How does this relate to cannabis use and psychosis?
Read the original research
Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat.
Schizophrenia research, 206, 263-270
Citation
Perez, Stephanie M; Donegan, Jennifer J; Boley, Angela M; Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J. (2019). Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat.. Schizophrenia research, 206, 263-270. https://doi.org/10.1016/j.schres.2018.11.006
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