Obsessive Compulsive and Impulse Control Disorders as an Analog for Addiction Pathogenesis

The purpose and focus of much of the current addiction research literature is identifying and elaborating on mechanisms which underpin the ‘switch’ from impulsive drug use to the compulsive seeking of the drug. Brewer and Potenza (2008) outline a pathogenesis of addiction akin to the development of impulse control disorders (ICD). In broad terms ICDs are described as behavioral addictions which traverse from goal-directed actions of active learning to habitualized responses (Brewer & Potenza, 2008). Everitt, Belin, Economidou, Peloux, Dalley, and Robbins (2008) describe the development of addiction as being parallel to that of obsessive-compulsive disorder. Generally, in their model, this transition occurs as part of a second-order schedule of reinforcement. Elements of Pavlovian conditioning result in the devaluation of the ultimate goal of initial drug use and the discriminative stimuli become the reinforcers keeping the behavior in place (Everitt et al., 2008).

While the behavioral pathologies of these ideas differ, the underlying neural mechanisms which assist in the ‘transition’ from casual to compulsive drug use share several characteristics. One of the best understood modes in which this happens is the switch from ventral striatum function over reward seeking to the dorsal striatum. According to Everitt et al. (2008) this switch also includes switches from prefrontal cortical to striatal control of drug taking and drug seeking. Using selective lesions, Everitt et al. (2008) found that the nucleus accumbens core (AcbC) is involved in drug seeking as lesions in this area significantly reduced cocaine seeking behavior. The researchers also used in vivo microdialysis to measure extracellular dopamine levels in rats that had received two months of second-order cocaine seeking training. Results demonstrated that after an extended amount of time where cocaine seeking was maintained by a second-order schedule dopamine release increased only in the dorsal striatum and not in the shell or core of the nucleus accumbens which comprise the ventral striatum (Everitt et al., 2008). Dorsal striatum involvement in maintenance of drug taking was decreased by dopamine blockage in that region, suggesting its importance in maintaining and seeking the drug (Everitt et al., 2008). For Everitt el al. the connection between instrumental, cue associated learning and the shift from ventral to dorsal striatal dopaminergic projections parallels OCD in that the original goal becomes devalued as the need to satiate the urge (compulsion) becomes more pervasive and the dorsolateral striatum more active.

Brewer and Potenza (2008) using pathological gambling as their primary example, demonstrate that impulsivity is increased when dopamine concentrations become higher in the dorsolateral striatum in comparison to the ventral regions. The distinction between Brewer’s ICD model and Everitt’s OCD model comes down to the role of 5-HT (serotonin) in decision making processes. While both authors acknowledge the importance of the prefrontal cortex in decision making and orbitofrontal cortex in reward evaluation, Brewer (2008) notes 5-HT and 5-HIAA processes as crucial in the functioning of the PFC and OFC themselves. They cite as evidence how alcoholism is associated with decreased behavioral inhibition mediated by tryptophan depletion (Brewer, 2008). Additionally they cite a Mehlman et al. (1994) study which demonstrated that 5-HIAA levels in monkeys was correlated to risk-taking behavior (Brewer, 2008). Using pathological gambling as their drug addiction-ICD connection, Brewer (2008) mention research where PFC lesions result in planning deficits, repeated negative consequence action taking, and low immediate rewards being taken over larger promised but delayed rewards. This ICD pathological framework of inability to see larger consequences bears striking resemblance to the framework of OCD except the OCD framework places larger emphasis on the devaluation of learned S-R relationships.

Further connecting ICDs and drug addiction Brewer (2008) note how poor performance on a color-word Stroop task is an observable outcome of hypoactivation in the OFC due to cocaine abuse. Everitt et al. (2008) cite Volkow et al. (2001) in associating reduced OFC activity with reduced D2/3 receptors in the striatum. This correlation projects onto the idea that cocaine addicts, because of their reduced inhibitory control, show “impaired probabilistic reversal learning” (Everitt et al., 2008). Simplified, this means that cocaine abusers will choose more risky outcomes because of problems with predicting or evaluating outcomes (Everitt et al., 2008). This sounds very similar to Brewer’s (2008) model of ICD and indeed many parallels can be drawn in terms of consequence evaluation deficits. The difference comes from Everitt et al.’s (2008) emphasis on negative reinforcement as characteristic in OCD and compulsive drug seeking. A model which Brewer (2008) calls “egodystonic” in the sense that the repetitive behaviors the individual participates are not found to be pleasurable or congruent with their sense of self. In contrast Brewer (2008) calls ICD repetitive behaviors egosyntonic in that they are often pleasurable and related to sensation-seeking whereas OCD is concerned with harm avoidance, i.e. avoiding the negative emotional state.

Finally drawing from Everitt and Robbins (2005), these themes can be tied together with what is described as “action-learning outcomes.” In this model NMDA injections or D1 receptor antagonist administered during training will prohibit the learning of Pavlovian responses whereas administration after training will disrupt the consolidation of the response into memory (Everitt & Robbins, 2005). This is relevant because it shows that instrumental learning and outcome devaluation occur in OCD whereas inability to learn about future consequences is associated with ICDs. It would follow then that the pathology of addiction encompasses both aspects of ICDs and OCD and can fit either conceptual framework. The common theme as it applies to behavior and underpinning neural bases is the shift from liking something originating in the ventral striatum to desiring something in the dorsal striatum.

 

REFERENCES

Brewer, J.A., & Potenza, M.N. (2008). The neurobiology and genetics of impulse control disorders: Relationships to drug addictions. Biochemical Pharmacology, 75(1), 63-75.

Everitt, B.J., & Robbins, T.W. (2005). Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nature Neuroscience. 8(11), 1481-1489.

Everitt, B.J., Belin, D., Economidou, D., Pelloux, Y., Dalley, J.W., & Robbins, T.W. (2008). Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philosophical transactions of the royal society B. 363(1507). 3125-3135.

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