Stress as a Common Risk Factor for Obesity and Addiction.

Stress as a Common Risk Factor for Obesity and Addiction.

Biol Psychiatry. 2013 Mar 26;
Sinha R, Jastreboff AM

Stress is associated with obesity, and the neurobiology of stress overlaps significantly with that of appetite and energy regulation. This review will discuss stress, allostasis, the neurobiology of stress and its overlap with neural regulation of appetite, and energy homeostasis. Stress is a key risk factor in the development of addiction and in addiction relapse. High levels of stress changes eating patterns and augments consumption of highly palatable (HP) foods, which in turn increases incentive salience of HP foods and allostatic load. The neurobiological mechanisms by which stress affects reward pathways to potentiate motivation and consumption of HP foods as well as addictive drugs is discussed. With enhanced incentive salience of HP foods and overconsumption of these foods, there are adaptations in stress and reward circuits that promote stress-related and HP food-related motivation as well as concomitant metabolic adaptations, including alterations in glucose metabolism, insulin sensitivity, and other hormones related to energy homeostasis. These metabolic changes in turn might also affect dopaminergic activity to influence food motivation and intake of HP foods. An integrative heuristic model is proposed, wherein repeated high levels of stress alter the biology of stress and appetite/energy regulation, with both components directly affecting neural mechanisms contributing to stress-induced and food cue-induced HP food motivation and engagement in overeating of such foods to enhance risk of weight gain and obesity. Future directions in research are identified to increase understanding of the mechanisms by which stress might increase risk of weight gain and obesity. HubMed – addiction


Ventral Striatum Binding of a Dopamine D2/3 Receptor Agonist But Not Antagonist Predicts Normal Body Mass Index.

Biol Psychiatry. 2013 Mar 27;
Caravaggio F, Raitsin S, Gerretsen P, Nakajima S, Wilson A, Graff-Guerrero A

BACKGROUND: Positron emission tomography research has shown that dopamine D2/3 receptor (D2/3R) availability is negatively correlated with body mass index (BMI) in obese but not in healthy subjects. However, previous positron emission tomography studies have not looked specifically at the ventral striatum (VS), which plays an important role in motivation and feeding. Furthermore, these studies have only used antagonist radiotracers. Normal-weight rats given free access to high-fat diets demonstrate behavioral sensitization to D2/3R agonists but not to antagonists. Sensitization is associated with increased D2/3R affinity, which affects binding of agonists but not antagonists. METHODS: We examined the association between BMI within the nonobese range (18.6-27.8) and D2/3R availability in the VS with the use of the agonist radiotracer [(11)C]-(+)-PHNO (n = 26) and the antagonist [(11)C]-raclopride (n = 35) in healthy humans. RESULTS: In the VS, we found a positive correlation between BMI and [(11)C]-(+)-PHNO binding but no relationship with [(11)C]-raclopride binding. Secondary analyses revealed no relationship between BMI and binding in the dorsal striatum with either radiotracer. CONCLUSIONS: We propose that in nonobese individuals, higher BMI may be associated with increased D2R affinity in the VS. This increased affinity may potentiate the incentive salience of food cues and counteract the effects of satiety cues, thereby increasing feeding. HubMed – addiction


Chemistry and Pharmacological Studies of 3-Alkoxy-2,5-Disubstituted-Pyridinyl Compounds as Novel Selective ?4?2 Nicotinic Acetylcholine Receptor Ligands That Reduce Alcohol Intake in Rats.

J Med Chem. 2013 Apr 1;
Liu Y, Richardson J, Tran T, Al-Muhtasib N, Xie T, Yenugonda VM, Sexton HG, Rezvani AH, Levin ED, Sahibzada N, Kellar KJ, Brown ML, Xiao Y, Paige M

Neuronal acetylcholine receptors mediate the addictive effects of nicotine and may also be involved in alcohol addiction. Varenicline, an approved smoking cessation medication, showed clear efficacy in reducing alcohol consumption in heavy-drinking smokers. More recently, sazetidine-A, which selectively desensitizes ?4?2 nicotinic receptors, was shown to significantly reduce alcohol intake in a rat model. To develop novel therapeutics for treating alcohol use disorder, we designed and synthesized novel sazetidine-A analogues containing a methyl group at the 2-position of the pyridine ring. In vitro pharmacological studies revealed that some of the novel compounds showed overall pharmacological property profiles similar to that of sazetidine-A but exhibited reduced agonist activity across all nicotinic receptor subtypes tested. In rat studies, compound (S)-9 significantly reduced alcohol uptake. More importantly, preliminary results from studies in a ferret model indicate that these novel nAChR ligands have an improved adverse side-effect profile in comparison with that of varenicline. HubMed – addiction


Polysubstance dependent patients display a more utilitarian profile in moral decision-making than alcohol-dependent patients, depressive patients and controls.

Drug Alcohol Depend. 2013 Mar 26;
Kornreich C, Brevers D, Ermer E, Hanak C, Verbanck P, Campanella S, Noël X

BACKGROUND: Addiction has been shown to be associated with the endorsement of utilitarian moral judgments. Ventro-medial prefrontal cortex (VMPFC) dysfunction may explain these findings. METHODS: 100 subjects were recruited: 25 polysubstance dependent patients, 25 alcohol dependent patients, 25 patients with major depressive disorders, and 25 normal controls. Subjects were assessed with a battery of 24 moral dilemmas: 8 impersonal dilemmas (no physical contact involved); 8 personal pareto (direct action that does not make the harmed individual worse off) and 8 personal non-pareto (direct action that does make the harmed individual worse off). The Iowa Gambling Task was used to document a possible connection between VMPFC dysfunction and responses to the moral dilemmas. RESULTS: Polysubstance dependent patients endorsed more utilitarian choices than controls on all types of dilemmas and more than depressed patients on impersonal and personal pareto dilemmas. Alcohol dependent patients had intermediate results between polysubstance dependent patients and controls but these differences were not significant. All patients showed significantly poorer performance compared to controls on the Iowa Gambling Task, but there was no significant association between Iowa Gambling Tasks scores and moral dilemma choices. CONCLUSION: Polysubstance dependent patients made more utilitarian choices when responding to moral dilemmas than depressed patients and normal controls, while alcoholic patients showed intermediate results. The absence of correlation between performance on the Iowa Gambling Task and the number of more utilitarian choices indicates that moral dilemma and decision making under uncertainty tap into separate mechanisms. HubMed – addiction


How to assess the role of transcranial magnetic stimulation in nicotine addiction.

Biol Psychiatry. 2013 Apr 15; 73(8): 702-3
Talih F, Nahas Z

HubMed – addiction