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 constructpreprint
Аннотация: Abstract 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 h/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.
Год издания: 2021
Авторы: Giordano de Guglielmo, Lieselot L. G. Carrette, Marsida Kallupi, Molly Brennan, Brent Boomhower, Lisa Maturin, Dana Conlisk, Sharona Sedighim, Lani Tieu, McKenzie J. Fannon, Angelica R. Martinez, Nathan Velarde, Dyar Othman, Ben Sichel, Jarryd Ramborger, Justin Kai‐Chi Lau, Jenni Kononoff, Adam Kimbrough, Sierra Simpson, Lauren C. Smith, Kokila Shankar, Sélène Bonnet-Zahedi, Elizabeth A. Sneddon, Alicia Avelar, Sonja L. Plasil, Joseph Mosquera, Caitlin Crook, Lucas Chun, Ashley Vang, Kristel K Milan, Paul Schweitzer, Bonnie Lin, Beverly Peng, Apurva S. Chitre, Oksana Polleskaya, Leah C. Solberg Woods, Abraham A. Palmer, Olivier George
Издательство: Cold Spring Harbor Laboratory
Источник: bioRxiv (Cold Spring Harbor Laboratory)
Ключевые слова: Neurotransmitter Receptor Influence on Behavior, Substance Abuse Treatment and Outcomes, Behavioral Health and Interventions
Открытый доступ: green