Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct.

Autor:	de Guglielmo G; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Carrette L; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Kallupi M; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Brennan M; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Boomhower B; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Maturin L; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Conlisk D; Department of Neuroscience, The Scripps Research Institute, La Jolla, San Diego, United States., Sedighim S; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Tieu L; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Fannon MJ; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Martinez AR; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Velarde N; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Othman D; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Sichel B; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Ramborger J; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Lau J; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Kononoff J; Department of Neuroscience, The Scripps Research Institute, La Jolla, San Diego, United States., Kimbrough A; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Simpson S; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Smith LC; Department of Psychiatry, University of California, San Diego, La Jolla, United States.; Department of Neuroscience, The Scripps Research Institute, La Jolla, San Diego, United States., Shankar K; Department of Psychiatry, University of California, San Diego, La Jolla, United States.; Department of Neuroscience, The Scripps Research Institute, La Jolla, San Diego, United States., Bonnet-Zahedi S; Department of Psychiatry, University of California, San Diego, La Jolla, United States.; Institut de Neurosciences de la Timone, Aix-Marseille Université, Marseille, France., Sneddon EA; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Avelar A; Department of Psychiatry, University of California, San Diego, La Jolla, United States.; Department of Neuroscience, The Scripps Research Institute, La Jolla, San Diego, United States., Plasil SL; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Mosquera J; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Crook C; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Chun L; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Vang A; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Milan KK; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Schweitzer P; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Lin B; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Peng B; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Chitre AS; Department of Psychiatry, University of California, San Diego, La Jolla, United States., Polesskaya O; Department of Psychiatry, University of California, San Diego, La Jolla, United States.; Institute for Genomic Medicine, University of California, San Diego, La Jolla, United States., Solberg Woods LC; Department of Internal Medicine, Section on Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, United States., Palmer AA; Department of Psychiatry, University of California, San Diego, La Jolla, United States.; Institute for Genomic Medicine, University of California, San Diego, La Jolla, United States., George O; Department of Psychiatry, University of California, San Diego, La Jolla, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Nov 01; Vol. 12. Date of Electronic Publication: 2024 Nov 01.
DOI:	10.7554/eLife.90422
Abstrakt:	Addiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences. However, the factors contributing to the transition from moderate drug use to these problematic patterns remain unclear, particularly regarding the role of sex. Many preclinical studies have been limited by small sample sizes, low genetic diversity, and restricted drug access, making it challenging to model significant levels of intoxication or dependence and translate findings to humans. To address these limitations, we characterized addiction-like behaviors in a large sample of >500 outbred heterogeneous stock (HS) rats using an extended cocaine self-administration paradigm (6 hr/daily). We analyzed individual differences in escalation of intake, progressive ratio (PR) responding, continued use despite adverse consequences (contingent foot shocks), and irritability-like behavior during withdrawal. Principal component analysis showed that escalation of intake, progressive ratio responding, and continued use despite adverse consequences loaded onto a single factor that was distinct from irritability-like behaviors. Categorizing rats into resilient, mild, moderate, and severe addiction-like phenotypes showed that females exhibited higher addiction-like behaviors, with a lower proportion of resilient individuals compared to males. These findings suggest that, in genetically diverse rats with extended drug access, escalation of intake, continued use despite adverse consequences, and PR responding are highly correlated measures of a shared underlying construct. Furthermore, our results highlight sex differences in resilience to addiction-like behaviors. Competing Interests: Gd, LC, MK, MB, BB, LM, DC, SS, LT, MF, AM, NV, DO, BS, JR, JL, JK, AK, SS, LS, KS, SB, ES, AA, SP, JM, CC, LC, AV, KM, PS, BL, BP, AC, OP, LS, AP, OG No competing interests declared (© 2023, de Guglielmo, Carrette et al.)
Databáze:	MEDLINE
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