Brittany N Kuhn1, Nazzareno Cannella2, Ayteria D Crow3, Analyse T Roberts3, Veronica Lunerti2, Carter Allen4, Rusty W Nall5, Gary Hardiman6, Leah C Solberg Woods7, Dongjun Chung4, Roberto Ciccocioppo2, Peter W Kalivas3. 1. Department of Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, BSB 403-MSC 510, Charleston, SC, 29425, USA. kuhnb@musc.edu. 2. School of Pharmacy, University of Camerino, Camerino, Italy. 3. Department of Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, BSB 403-MSC 510, Charleston, SC, 29425, USA. 4. Department of Biomedical Informatics, The Ohio State University, Columbus, OH, USA. 5. Department of Psychology, Jacksonville State University, Jacksonville, AL, USA. 6. School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK. 7. Department of Internal Medicine, Wake Forest University, Winston-Salem, NC, USA.
Abstract
RATIONALE: The ongoing rise in opioid use disorder (OUD) has made it imperative to better model the individual variation within the human population that contributes to OUD vulnerability. Using animal models that capture such variation can be a useful tool. Individual variation in novelty-induced locomotion is predictive of substance use disorder (SUD) propensity. In this model, rats are characterized as high-responders (HR) or low-responders (LR) using a median split based on distance travelled during a locomotor test, and HR rats are generally found to exhibit a more SUD vulnerable behavioral phenotype. OBJECTIVES: The HR/LR model has commonly been used to assess behaviors in male rats using psychostimulants, with limited knowledge of the predictive efficacy of this model in females or the use of an opioid as the reward. In the current study, we assessed several behaviors across the different phases of drug addiction (heroin taking, refraining, and seeking) in over 500 male and female heterogeneous stock rats run at two geographically separate locations. Rats were characterized as HRs or LRs within each sex for analysis. RESULTS: Overall, females exhibit a more OUD vulnerable phenotype relative to males. Additionally, the HR/LR model was predictive of OUD-like behaviors in male, but not female rats. Furthermore, phenotypes did not differ in anxiety-related behaviors, reacquisition of heroin-taking, or punished heroin-taking behavior in either sex. CONCLUSIONS: These results emphasize the importance of assessing females in models of individual variation in SUD and highlight limitations in using the HR/LR model to assess OUD propensity.
RATIONALE: The ongoing rise in opioid use disorder (OUD) has made it imperative to better model the individual variation within the human population that contributes to OUD vulnerability. Using animal models that capture such variation can be a useful tool. Individual variation in novelty-induced locomotion is predictive of substance use disorder (SUD) propensity. In this model, rats are characterized as high-responders (HR) or low-responders (LR) using a median split based on distance travelled during a locomotor test, and HR rats are generally found to exhibit a more SUD vulnerable behavioral phenotype. OBJECTIVES: The HR/LR model has commonly been used to assess behaviors in male rats using psychostimulants, with limited knowledge of the predictive efficacy of this model in females or the use of an opioid as the reward. In the current study, we assessed several behaviors across the different phases of drug addiction (heroin taking, refraining, and seeking) in over 500 male and female heterogeneous stock rats run at two geographically separate locations. Rats were characterized as HRs or LRs within each sex for analysis. RESULTS: Overall, females exhibit a more OUD vulnerable phenotype relative to males. Additionally, the HR/LR model was predictive of OUD-like behaviors in male, but not female rats. Furthermore, phenotypes did not differ in anxiety-related behaviors, reacquisition of heroin-taking, or punished heroin-taking behavior in either sex. CONCLUSIONS: These results emphasize the importance of assessing females in models of individual variation in SUD and highlight limitations in using the HR/LR model to assess OUD propensity.
Authors: Marilyn E Carroll; Andrew D Morgan; Wendy J Lynch; Una C Campbell; Nancy K Dess Journal: Psychopharmacology (Berl) Date: 2002-03-27 Impact factor: 4.530
Authors: Stephanie M Y Wong; Y N Suen; Charlotte W C Wong; Sherry K W Chan; Christy L M Hui; W C Chang; Edwin H M Lee; Calvin P W Cheng; Garrett C L Ho; Gladys Goh Lo; Eric Y L Leung; Paul K M Au Yeung; Sirong Chen; William G Honer; Henry K F Mak; P C Sham; Peter J McKenna; Edith Pomarol-Clotet; Mattia Veronese; Oliver D Howes; Eric Y H Chen Journal: Psychopharmacology (Berl) Date: 2022-02-25 Impact factor: 4.530