Context-induced relapse after voluntary abstinence
Substance abuse is a major health care problem. Accordingly, there is a real need to increase our fundamental understanding of the processes behind addiction, so that more targeted therapeutic strategies can follow.
We aim to further unravel the brain mechanisms of relapse to alcohol seeking, and will identify novel brain areas and circuits that future clinical studies can target in treatment-seeking alcoholics.
A limitation identified in animal models is that abstinence is achieved ‘non-voluntarily’ (experimenter-imposed). In humans, however, abstinence is typically voluntary (self-imposed), despite drug availability and often out of a desire to avoid the negative consequence associated with excessive alcohol use. Dr Nathan Marchant recently developed an animal model which addresses this limitation. In this model, the laboratory animal abstains voluntarily from alcohol use when alcohol-seeking is associated with a negative consequence.
Dr Marchant has provided the first evidence that context-induced relapse of alcohol seeking after punishment-imposed abstinence is associated with increased activity in a three nucleus circuit comprising of the ventral subiculum projection to nucleus accumbens shell, which projects to lateral hypothalamus. In addition we have extensively validated a novel dual-virus (DREADD-based) approach that enables bi-directional control of activity in neural populations defined by their anatomical projections. We will combine this novel animal model of relapse with an innovative procedure to manipulate neurons in defined neural circuits to determine:
- Which Nucleus Accumbens (NAc) shell output is critical for context-induced relapse to alcohol seeking?
- What is the receptor expression profile of NAc shell neurons projecting to Lateral Hypothalamus?
- Which glutamatergic input to NAc shell is critical for context-induced relapse to alcohol seeking?
Outcomes & Significance: We have identified a potentially critical neural mechanism by which alcohol associated environments promote alcohol seeking during abstinence.
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