Common cellular and molecular mechanisms in obesity and drug addiction
Key Points Common brain sites and neurotransmitter systems are activated in response to palatable food and drugs of abuse. Addictive drugs seem to be particularly effective in stimulating the very same brain systems whose function is to process information related to food palatability and regulate t...
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Veröffentlicht in: | Nature reviews. Neuroscience 2011-11, Vol.12 (11), p.638-651 |
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Common brain sites and neurotransmitter systems are activated in response to palatable food and drugs of abuse. Addictive drugs seem to be particularly effective in stimulating the very same brain systems whose function is to process information related to food palatability and regulate the incentive value of food.
The nucleus tractus solitarius (NTS) receives input related to food palatability from the mouth and gastrointestinal tract. Circulating hormonal regulators of hunger and satiety also influence NTS activity. The NTS contains at least three distinct populations of neurons, those containing catecholamines, proopiomelanocortin (POMC) or glucagon-like peptide 1 (GLP1; a cleavage product of glucagon). The NTS seems to play a key part in drug reward and also in some aspects of drug withdrawal.
The insular cortex encodes and stores information related to the valence and magnitude of food and drug reward. In particular, the insula seems to play an important part in contrasting the palatability of currently and previously available food or drug reinforcers and thereby determining if there has been a change in the relative value of food or drug reinforcers.
The orbitofrontal cortex (OFC) processes information about the relative motivational value of palatable food or addictive drugs at any given time based on information from metabolic or hedonic circuitries in the brain. As such, the OFC seems to have a key role in the development of satiety.
The striatum, and in particular dopamine, opioid and cannabinoid systems within the striatum, encode information related to the appetitive and incentive value of food and drugs of abuse.
Palatable food and drugs of abuse can trigger common molecular adaptations in brain reward systems, including increases in the transcription factor ΔFOSB. Such neuroadaptive responses are likely to contribute to the development of obesity and addiction.
Brain inflammatory responses have been implicated in the development of obesity and drug addiction. The transcription factor nuclear factor-κB (NF-κB) in particular may have a key role in driving excessive food or drug intake.
New areas of research in obesity and drug addiction include assessing the role for neurogenesis in the adult brain and the involvement of nuclear hormone receptors like peroxisome proliferator-activated receptor-γ (PPARγ). In addition, gene regulatory processes including DNA methylation and chromatin modifications, and post-transcriptional gene regula |
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ISSN: | 1471-003X 1471-0048 1469-3178 |
DOI: | 10.1038/nrn3105 |