Abstract
The DSM5-based dimensional diagnostic approach defines substance use disorders on a continuum from recreational drug use to habitual and ultimately addicted behavior. Biomarkers that are indicative of recreational drug use and addicted behavior are lacking. We performed a translational [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) study in the multi-dimensional 0/3crit model of cocaine addiction. Addict-like (3crit) and non-addict-like (0crit) rats, which shared identical life conditions and levels of cocaine self-administration, were acquired for FDG-PET under baseline conditions and following cocaine and yohimbine challenges. Compared to cocaine-naïve control rats, 0crit animals showed higher glucose uptake in the caudate putamen (CPu) and medial prefrontal cortex (mPFC) respect to naïve controls. 3crit animals did not show this adaptive higher glucose utilization, but had lower uptake in several cortical areas. Both cocaine and yohimbine challenges affected glucose uptake in control rats in several brain sites, but not in 0crit and 3crit rats, indicating that impaired glucose mobilization in response to these challenges is not specifically associated with addictive behavior. Compared to 0crit, 3crit rats showed higher reinstatement responses, which were negatively associated with glucose uptake in the ventral tegmental area. Data indicate that cocaine non-addict- and addict-like phenotypes are associated with several potential biomarkers. Specifically, we propose that increased glucose uptake in the CPu and mPFC is a function of controlled drug use, whereas a loss of striatal and prefrontal metabolic activity and reduced uptake in cortical areas are indicative of addictive behavior.
Highlights
Cocaine addiction is a psychiatric disorder characterized by the maintenance of drug use despite detrimental consequences
We subjected rats characterized for addict-like and nonaddict-like behavior and age-matched cocaine-naïve control rats to fluorodeoxyglucose-positron emission tomography (FDG-positron emission tomography (PET)) acquisition to study alterations in glucose uptake associated with non-addicit- vs addict-like drug intake resulting from cocaine-taking behavior
This result is in line with human data showing reduced frontal glucose metabolism in cocaine addicted patients [3, 4], supporting the construct validity of the 0/3crit animal model for cocaine addiction
Summary
Cocaine addiction is a psychiatric disorder characterized by the maintenance of drug use despite detrimental consequences. In contrast to clinical studies on drug-related cues, ethical concerns hamper human studies on the effect of cocaine challenges to drug-naïve subjects [10] This limits the understanding of the physiological and abnormal responses to drugs, as healthy drug users are usually chosen as controls. Another drawback of FDG-PET studies conducted to date is the lack of non-addict drug user controls that allow the disentangling of adaptations associated with loss of control from controlled cocaine use. Such a comparison is critical for the identification of potential biomarkers
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