Neuron Navigator 1 (Nav1) regulates the response to cocaine in mice
Jared R Bagley1, Yalun Tan2, Wan Zhu2
1Department of Psychology, Binghamton University, Binghamton, NY, USA.
Communications Biology
|October 18, 2023
Summary
Genetic factors influence substance use disorders. Deleting the Nav1 gene in mice increased cocaine intake and altered brain synapses, suggesting Nav1 impacts drug response.
Area of Science:
- Neurogenetics
- Molecular Neuroscience
- Behavioral Neuroscience
Background:
- Genetic variation significantly contributes to substance use disorder (SUD) risk, yet specific genes and mechanisms remain largely unidentified.
- Heritable differences in voluntary cocaine self-administration exist across inbred mouse strains, providing a model for genetic investigation.
Purpose of the Study:
- To identify genetic factors influencing cocaine self-administration and investigate their underlying mechanisms.
- To test the hypothesis that Nav1, a neuron navigator gene, plays a role in regulating cocaine intake.
Main Methods:
- Computational genetic analysis of cocaine self-administration data from 21 inbred mouse strains.
- Generation and characterization of Nav1 knockout mice.
- Immunohistochemistry, electrophysiology, and transcriptomic analyses to explore molecular mechanisms.
Main Results:
- Computational analysis identified Nav1 as a candidate gene for cocaine self-administration.
- Nav1 knockout mice displayed significantly increased voluntary cocaine intake and motivation for cocaine.
- Nav1 deficiency led to reduced cortical inhibitory synapse density, enhanced cortical and hippocampal excitatory transmission, and increased deep cortical excitatory neurons.
Conclusions:
- Nav1 plays a crucial role in regulating behavioral responses to cocaine.
- Nav1 knockout-induced alterations in cortical and hippocampal excitatory-inhibitory balance may underlie the observed increase in cocaine consumption.
