The association of plasma acyl ghrelin level with alcohol craving in early abstinent alcohol dependent patients

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

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The association of the appetitive peptide acetylated ghrelin with alcohol craving in early abstinent alcohol dependent individuals

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2011.11.005 ◽

2012 ◽

Vol 37 (7) ◽

pp. 980-986 ◽

Cited By ~ 50

Author(s):

Anne Koopmann ◽

Christoph von der Goltz ◽

Martin Grosshans ◽

Christina Dinter ◽

Meike Vitale ◽

...

Keyword(s):

Alcohol Craving ◽

Alcohol Dependent

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Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving

Journal of Psychopharmacology ◽

10.1177/0269881117691455 ◽

2017 ◽

Vol 31 (7) ◽

pp. 883-892 ◽

Cited By ~ 10

Author(s):

Helen C Fox ◽

Verica Milivojevic ◽

Gustavo A Angarita ◽

Raymond Stowe ◽

Rajita Sinha

Keyword(s):

Immune System ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Negative Mood ◽

Alcohol Group ◽

Alcohol Craving ◽

Peripheral Immune System ◽

Time Points ◽

Necrosis Factor ◽

Alcohol Dependent

Background: Peripheral immune system cytokines may play an integral role in the underlying sensitized stress response and alcohol craving during early alcohol withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. Methods: A total of 39 early abstinent, treatment-seeking, alcohol-dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. Results: The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. Conclusions: Findings demonstrate that broad immunosuppression is still observed in alcohol-dependent individuals after 3 weeks of abstinence and may be linked to motivation for alcohol.

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