Insulin signaling and addiction

NEUROPHARMACOLOGY

卷:61

Review

Daws, Lynette C.²  Avison, Malcolm J.³  Robertson, Sabrina D.⁴  Niswender, Kevin D.^5,6  Galli, Aurelio¹  Saunders, Christine⁷ 

[1] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Mol Neurosci, Sch Med, Nashville, TN 37232 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA

[3] Vanderbilt Univ, Sch Med, Inst Imaging Sci, Nashville, TN 37232 USA

[4] Natl Inst Environm Hlth, Dev Neurobiol Lab, Res Triangle Pk, NC USA

[5] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA

[6] Tennessee Valley Healthcare Syst, Nashville, TN USA

[7] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA

关键词: Insulin;    Dopamine;    Dopamine transporter;    Amphetamine;    Obesity;   

DOI  :  10.1016/j.neuropharm.2011.02.028

来源: Elsevier

【 摘 要 】

Across species, the brain evolved to respond to natural rewards such as food and sex. These physiological responses are important for survival, reproduction and evolutionary processes. It is no surprise, therefore, that many of the neural circuits and signaling pathways supporting reward processes are conserved from Caenorhabditis elegans to Drosophilae, to rats, monkeys and humans. The central role of dopamine (DA) in encoding reward and in attaching salience to external environmental cues is well recognized. Less widely recognized is the role of reporters of the internal environment, particularly insulin, in the modulation of reward. Insulin has traditionally been considered an important signaling molecule in regulating energy homeostasis and feeding behavior rather than a major component of neural reward circuits. However, research over recent decades has revealed that DA and insulin systems do not operate in isolation from each other, but instead, work together to orchestrate both the motivation to engage in consummatory behavior and to calibrate the associated level of reward. Insulin signaling has been found to regulate DA neurotransmission and to affect the ability of drugs that target the DA system to exert their neurochemical and behavioral effects. Given that many abused drugs target the DA system, the elucidation of how dopaminergic, as well as other brain reward systems, are regulated by insulin will create opportunities to develop therapies for drug and potentially food addiction. Moreover, a more complete understanding of the relationship between DA neurotransmission and insulin may help to uncover etiological bases for food addiction and the growing epidemic of obesity. This review focuses on the role of insulin signaling in regulating DA homeostasis and DA signaling, and the potential impact of impaired insulin signaling in obesity and psychostimulant abuse. This article is part of a Special Issue entitled 'Synaptic Plasticity and Addiction'. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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