Do gene expression findings from mouse models of cocaine use recapitulate human cocaine use disorder in reward circuitry?

Autor: Huggett SB; Behavioral Genetics of Addiction Laboratory, Department of Psychology at Emory University, Atlanta, Georgia, USA., Bubier JA; Center for Systems Neurogenetics of Addiction, The Jackson Laboratory, Bar Harbor, Maine, USA., Chesler EJ; Center for Systems Neurogenetics of Addiction, The Jackson Laboratory, Bar Harbor, Maine, USA., Palmer RHC; Behavioral Genetics of Addiction Laboratory, Department of Psychology at Emory University, Atlanta, Georgia, USA.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2021 Feb; Vol. 20 (2), pp. e12689. Date of Electronic Publication: 2020 Sep 15.
DOI: 10.1111/gbb.12689
Abstrakt: Animal models of drug use have investigated possible mechanisms governing human substance use traits for over 100 years. Most cross-species research on drug use/addiction examines behavioral overlap, but studies assessing neuromolecular (e.g. RNA) correspondence are lacking. Our study utilized transcriptome-wide data from the hippocampus and ventral tegmental area (VTA)/midbrain from a total of 35 human males with cocaine use disorder/controls and 49 male C57BL/6J cocaine/saline administering/exposed mice. We hypothesized differential expressed genes and systems of co-expressed genes (gene networks) would show appreciable overlap across mouse cocaine self-administration and human cocaine use disorder. We found modest, but significant relationships between differentially expressed genes associated with cocaine self-administration (short access) and cocaine use disorder within reward circuitry. Differentially expressed genes underlying models of acute cocaine exposure (cocaine), context re-exposure and cocaine + context re-exposure were not consistently associated with human CUD across brain regions. Investigating systems of co-expressed genes, we found several validated gene networks with weak to moderate conservation between cocaine/saline self-administering mice and disordered cocaine users/controls. The most conserved hippocampal and VTA gene networks demonstrated substantial overlap (2029 common genes) and included both novel and previously implicated targets for cocaine use/addiction. Lastly, we conducted (expression-based) phenome-wide association studies of the nine common hub genes across conserved gene networks. Common hub genes were associated with dopamine/serotonin function, cocaine self-administration and other relevant mouse traits. Overall, our study pinpointed and characterized conserved brain-related RNA patterns across mouse cocaine self-administration and human cocaine use disorder. We offer recommendations for future research and add to the dialogue surrounding pre-clinical animal research for human disease.
(© 2020 International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje