Shared brain vulnerabilities open the way for nonsubstance addictions: Carving addiction at a new joint?

Division of Clinical Neuroscience and Behavioral Research, National Institute on Drug Abuse, Rockville, Maryland, USA.
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 02/2010; 1187(1):294-315. DOI: 10.1111/j.1749-6632.2009.05420.x
Source: PubMed

ABSTRACT For more than half a century, since the beginning of formal diagnostics, our psychiatric nosology has compartmentalized the compulsive pursuit of substance (e.g., alcohol, cocaine, heroin, nicotine) from nonsubstance (e.g., gambling, food, sex) rewards. Emerging brain, behavioral, and genetic findings challenge this diagnostic boundary, pointing to shared vulnerabilities underlying the pathological pursuit of substance and nonsubstance rewards. Working groups for the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), are thus considering whether the nosologic boundaries of addiction should be redrawn to include nonsubstance disorders, such as gambling. This review discusses how neurobiological data from problem gambling, obesity, and "normal" states of attachment (romantic infatuation, sexual attraction, maternal bonds) may help us in the task of carving addictions "at a new joint." Diagnostic recarving may have a positive effect on addiction research, stimulating discovery of "crossover" pharmacotherapies with benefit for both substance and nonsubstance addictions.

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Available from: Joseph Frascella, Sep 29, 2015
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    • "A growing literature suggests that excessive and compulsive eating has much in common with drug addiction, including behavioral phenotypes and underlying physiological and neuroanatomical mechanisms (Frascella et al. 2010; Gearhardt et al. 2011; Kenny 2011; Volkow et al. 2012). Although it is clear that eating disorders are enormously heterogeneous, and that the addiction model has its limitations (Epstein & Shaham 2010; Ziauddeen, Farooqi & Fletcher 2012), it is nonetheless relevant that, similar to abstinence among drug addicts, dieting among individuals attempting to reduce their palatable food intake is associated with high rates of relapse (Kramer et al. 1989; Skender et al. 1996). "
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    ABSTRACT: Acute exposure to the pharmacological stressor yohimbine induces relapse to both food and drug seeking in a rat model. However, no systematic studies on the effects of chronic stress on relapse have been conducted. Because chronic stress causes changes in dopamine D1 -like receptor-mediated transmission in prefrontal cortex (a relapse node), we tested the hypothesis that chronic exposure to stress increases vulnerability to relapse via dopamine-mediated mechanisms. Additionally, to determine the role of food-conditioned cues in reinstatement of food seeking, we made discrete food-paired cues either available (CS Present) or not available (CS Absent) during extinction and reinstatement testing. Rats responded for palatable food reinforcers in daily 3-hour sessions, and the behavior was extinguished. To model chronic stress, rats were injected daily with yohimbine (0.0, 2.5, or 5.0 mg/kg; i.p.) during the first 7 days of extinction. Injections were combined with SCH-23390 (0.0, 5.0, or 10.0 µg/kg; i.p.), a D1 -like receptor antagonist. Rats were then tested for reinstatement of food seeking triggered by acute yohimbine (0.0, 1.0, or 2.0 mg/kg; i.p.) and pellet priming. Rats treated previously with chronic yohimbine displayed increased responding following acute yohimbine priming relative to non-chronically stressed rats, but in the CS Absent condition only. Conversely, the lower dose of chronic yohimbine caused an increase in pellet-primed reinstatement, but this effect was more pronounced in the CS Present condition. Importantly, SCH-23390 combined with repeated yohimbine injections attenuated these effects. Thus, chronic stress may increase vulnerability to relapse under specific circumstances via a dopamine D1 -like receptor-mediated mechanism. © 2015 Society for the Study of Addiction.
    Addiction Biology 07/2015; DOI:10.1111/adb.12287 · 5.36 Impact Factor
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    • "Among the behavioral concomitants are increased rewarding effects of D1 receptor agonists and psychostimulant drugs, and resistance to extinction of a cocaine-conditioned place preference acquired during a prior ad libitum-fed (AL) state (Cabeza de Vaca and Carr, 1998; Zheng et al., 2013). In light of evidence that drug addiction represents a ''hijacking'' of the neurocircuitry that mediates appetitively motivated behavior (Kelley and Berridge, 2002; Cardinal and Everitt, 2004; Di Chiara, 2005; Volkow et al., 2008; Davis and Carter, 2009; Frascella et al., 2010), the enhanced responsiveness to drugs and associated cues during FR likely reflect 0306-4522/Ó 2015 IBRO. Published by Elsevier Ltd. "
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    ABSTRACT: Weight-loss dieting often leads to loss of control, rebound weight gain, and is a risk factor for binge pathology. Based on findings that food restriction (FR) upregulates sucrose-induced trafficking of glutamatergic AMPA receptors to the nucleus accumbens (NAc) postsynaptic density (PSD), this study was an initial test of the hypothesis that episodic "breakthrough" intake of forbidden food during dieting interacts with upregulated mechanisms of synaptic plasticity to increase reward-driven feeding. Ad libitum (AL) fed and FR subjects consumed a limited amount of 10% sucrose, or had access to water, every other day for ten occasions. Beginning three weeks after return of FR rats to AL feeding, when 24-hour chow intake and rate of body weight gain had normalized, subjects with a history of sucrose intake during FR consumed more sucrose during a four week intermittent access protocol than the two AL groups and the group that had access to water during FR. In an experiment that substituted noncontingent administration of d-amphetamine for sucrose, FR subjects displayed an enhanced locomotor response during active FR but a blunted response, relative to AL subjects, during recovery from FR. This result suggests that the enduring increase in sucrose consumption is unlikely to be explained by residual enhancing effects of FR on dopamine signaling. In a biochemical experiment which paralleled the sucrose behavioral experiment, rats with a history of sucrose intake during FR displayed increased abundance of pSer845-GluA1, GluA2, and GluA3 in the NAc PSD relative to rats with a history of FR without sucrose access and rats that had been AL throughout, whether they had a history of episodic sucrose intake or not. A history of FR, with or without a history of sucrose intake, was associated with increased abundance of GluA1. A terminal 15-min bout of sucrose intake produced a further increase in pSer845-GluA1 and GluA2 in subjects with a history of sucrose intake during FR. Generally, neither a history of sucrose intake nor a terminal bout of sucrose intake affected AMPA receptor abundance in the NAc PSD of AL subjects. Together, these results are consistent with the hypothesis, but the functional contribution of increased synaptic incorporation of AMPA receptors remains to be established. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience 03/2015; 295. DOI:10.1016/j.neuroscience.2015.03.025 · 3.36 Impact Factor
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    • "Over the same time period, measures of physical activity have decreased and caloric intake has risen, indicating an increase in non-homeostatic eating [23]. Consuming excessive amounts of energy-dense, highly palatable foods contributes to obesity onset and maintenance [12]. It has been suggested that highly palatable foods may be more reinforcing in obese than in lean individuals, thus enhancing vulnerability for over-eating (see [39] for review). "
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    ABSTRACT: Obesity is associated with abnormal brain reactivity in response to palatable food consumption, a factor that may contribute to non-homeostatic eating. However, little is known about how obesity interacts with the reinforcing effects of highly palatable constituents of food (e.g., fat), and if altered reinforcement processes associated with obesity generalize to non-food reinforcers. The current study compared the reinforcing effects of a fat (corn oil) and a drug of abuse (cocaine) in obese and lean Zucker rats. Specifically, obese and lean Zucker rats self-administered corn oil or intravenous cocaine in a behavioral economic demand procedure. For corn oil, maximum demand was higher and demand elasticity was lower in the obese rats compared to their lean counterparts. However, there were no differences in demand for cocaine between the obese and lean rats. These results demonstrate that a fat in the form of corn oil is a more effective reinforcer in obese Zucker rats. However, the fact that demand for cocaine was not different between the obese and lean rats suggests that differences in reward mechanisms may be reinforcer-specific and do not necessarily generalize to non-food reinforcers. Copyright © 2015. Published by Elsevier Inc.
    Physiology & Behavior 03/2015; 143. DOI:10.1016/j.physbeh.2015.03.002 · 2.98 Impact Factor
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