Pavlovian Response May Be In the Nucleus Accumbens of Addicts

A Critical Component to Hedonically-Driven, Pavlovian Response Among Persons with SUDs May Be In the Nucleus Accumbens

The ability to form associations between predictive rewarding events or outcomes is a fundamental aspect of learned behavior. This seemingly simple Pavlovian ability involves complex neural processing that has developed as a result of both environmental stimuli and from normal maturation to identify, seek, and use natural rewards that are based on updated sensory information.

Emerging evidence from both animal and human research suggests that this type of processing is mediated in part by the nucleus accumbens (NAc). The NAc is required for a number of reward-related behaviors and processes specific information about reward salience, availability, time estimates, value, and context. In addition, this nuclei is critical for the acquisition and expression of most Pavlovian stimulus-reward relationships, where cues that predict rewards produce robust changes in neural activity and notably so in the NAc. This Pavlovian anticipatory reward system has also been implicated in human drug addiction, including the ability of drug-paired cues to direct and control behavior.

Ask the ExpertThe authors of this important research utilized local field potential (LFP) recordings from both mouse and human NAc during a period of reward anticipation, to find prominent delta oscillations elicited during the time between anticipatory reward and behavioral change. The investigators found that through the use of responsive neurostimulation (RNS), increasing the electrical stimulation from 1- to 4-Hz oscillations during drug reward anticipation, a consummatory reduction in behavior in mice sensitized to highly palatable food occurred. Because similar oscillations are present in human NAc during reward anticipation, it is hoped that the translational potential of these findings may result in the development of a novel treatment for a major unmet need in the field of addictive disease.

Why Does This Matter?

Drug taking stimulates and begets drug taking via neuronal degradation of inhibitory control over time. Brain stimulation approaches have shown encouraging results for many neuropsychiatric conditions and may be effective in mediation of neuroadaptive changes associated with SUDs.

Addictive disease affects over 40 million Americans (23 million addicts plus their families). The relapse rate during the first few months post treatment is high and related to drug stimulus and drug craving. Medically Assisted Treatment has benefited many individuals, but not so much in far too many others. A new and novel approach, as described in this current research suggests that mediating both biological and environmentally triggered and rewarding Pavlovian anticipatory cues is a viable pursuit and is desperately needed. Non pharmacological interventions such as targeted brain stimulation could potentially be a game changer for millions of suffering addicts and their families.

Wu, H. Et al. Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man. Proc Natl Acad Sci U S A. 2017 Dec 18. pii: 201712214. doi: 10.1073/pnas.1712214114. [Epub ahead of print]