Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats
- PDF / 1,752,633 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 89 Downloads / 210 Views
ORIGINAL INVESTIGATION
Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats A. F. Garcia 1,2 & I. G. Webb 1 & L. M. Yager 1 & M. B. Seo 1 & S. M. Ferguson 1,2,3 Received: 11 December 2019 / Accepted: 8 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Drug addiction is a chronic disease defined by a complex set of characteristics, including loss of control over drug intake and persistent drug craving, which primarily affects a small percentage of people who try drugs. Although many models have been developed to study individual aspects of drug use, there is great translational value in having an animal model that encompasses multiple aspects of the human disease, including the variation in severity observed in humans. Here, we describe an intermittent access model of cocaine self-administration that produces a subset of rats that display many of the core features of addiction, including escalation of drug intake, a binge-like pattern of drug use, robust locomotor sensitization, and high levels of drugseeking during cue-induced reinstatement. This group is compared with rats that have the same drug history but do not develop this pattern of drug-taking and drug-seeking, as well as rats that undergo a traditional continuous access paradigm. Finally, we observe that high levels of cocaine consumption produce long-term changes in intracellular calcium signaling in the dorsomedial striatum. Keywords Cocaine . Drug addiction . Dorsomedial striatum
Introduction Drug addiction is a chronic, relapsing disease that carries high costs to both individuals and society through its effects on quality of life, productivity, healthcare, and crime (Cartwright 2008; Leshner 1997; Robbins and Everitt 1999). Although drug use is common, only a relatively small number of individuals who try drugs ever develop a substance use disorder (Anthony et al. 1994; Penberthy et al. 2010; Grant and Dawson 1998). Nonetheless, it is not well-understood why some drug users transition to addiction and others do not. Determining the neural correlates of addiction will help us to address this critical issue; however, it is necessary to first be able to effectively and accurately model in animals the
* S. M. Ferguson [email protected] 1
Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA, USA
2
Neuroscience Graduate Program, University of Washington, Seattle, WA, USA
3
Department of Psychiatry and Behavioral Sciences, Alcohol and Drug Abuse Institute, University of Washington, Seattle, WA, USA
subset of individuals susceptible to drug addiction. This is a challenging task, as addiction is composed of a constellation of symptoms, including compulsive drug-taking and drugseeking, loss of control over drug intake which leads to binges, and a persistent, sensitized craving for the drug. Over the years, a range of models have been used to capture key features of addiction. For example, non-contingent models such as locom
Data Loading...
