Treatment-Enhanced Paired Action Contributes Substantially to Change Across Multiple Health Behaviors: Secondary Analyses of Five Randomized Trials.

Treatment-enhanced paired action contributes substantially to change across multiple health behaviors: secondary analyses of five randomized trials.

Transl Behav Med. 2013 Mar 1; 3(1): 62-71
Yin HQ, Prochaska JO, Rossi JS, Redding CA, Paiva AL, Blissmer B, Velicer WF, Johnson SS, Kobayashi H

The dominant paradigm of changing multiple health behaviors (MHBs) is based on treating, assessing, and studying each behavior separately. This study focused on individuals with co-occurring baseline health-risk behavior pairs and described whether they changed over time on both or only one of the behaviors within each pair. Data from five randomized trials of computer-tailored interventions (CTIs) that simultaneously treated MHBs were analyzed. The differences between treatment and control proportions that achieved paired action and singular action at 24 months follow-up, and the proportional contribution of paired action to overall change on each behavior, were assessed across 12 behavior pairs (including energy balance, addictive, and appearance-related behaviors). CTIs consistently produced more paired action across behavior pairs. Paired action contributed substantially more to the treatment-related outcomes than singular action. Studying concurrent changes on MHBs as demonstrated allows the effect of simultaneously treating MHBs to be assessed. HubMed – addiction


Regulator of G protein signaling is a crucial modulator of antidepressant drug action in depression and neuropathic pain models.

Proc Natl Acad Sci U S A. 2013 Apr 29;
Stratinaki M, Varidaki A, Mitsi V, Ghose S, Magida J, Dias C, Russo SJ, Vialou V, Caldarone BJ, Tamminga CA, Nestler EJ, Zachariou V

Regulator of G protein signaling 4 (Rgs4) is a signal transduction protein that controls the function of monoamine, opiate, muscarinic, and other G protein-coupled receptors via interactions with G? subunits. Rgs4 is expressed in several brain regions involved in mood, movement, cognition, and addiction and is regulated by psychotropic drugs, stress, and corticosteroids. In this study, we use genetic mouse models and viral-mediated gene transfer to examine the role of Rgs4 in the actions of antidepressant medications. We first analyzed human postmortem brain tissue and found robust up-regulation of RGS4 expression in the nucleus accumbens (NAc) of subjects receiving standard antidepressant medications that target monoamine systems. Behavioral studies of mice lacking Rgs4, including specific knockdowns in NAc, demonstrate that Rgs4 in this brain region acts as a positive modulator of the antidepressant-like and antiallodynic-like actions of several monoamine-directed antidepressant drugs, including tricyclic antidepressants, selective serotonin reuptake inhibitors, and norepinephrine reuptake inhibitors. Studies using viral-mediated increases in Rgs4 activity in NAc further support this hypothesis. Interestingly, in prefrontal cortex, Rgs4 acts as a negative modulator of the actions of nonmonoamine-directed drugs that are purported to act as antidepressants: the N-methyl-D-aspartate glutamate receptor antagonist ketamine and the delta opioid agonist (+)-4-[(?R)-?-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide. Together, these data reveal a unique modulatory role of Rgs4 in the brain region-specific actions of a wide range of antidepressant drugs and indicate that pharmacological interventions at the level of RGS4 activity may enhance the actions of such drugs used for the treatment of depression and neuropathic pain. HubMed – addiction


Smoking but not cocaine use is associated with lower cerebral metabotropic glutamate receptor 5 density in humans.

Mol Psychiatry. 2013 Apr 30;
Hulka LM, Treyer V, Scheidegger M, Preller KH, Vonmoos M, Baumgartner MR, Johayem A, Ametamey SM, Buck A, Seifritz E, Quednow BB

Long-lasting neuroadaptations in the glutamatergic corticostriatal circuitry have been suggested to be responsible for the persisting nature of drug addiction. In particular, animal models have linked the metabotropic glutamate receptor 5 (mGluR5) to drug-seeking behavior and extinction learning. Accordingly, blocking mGluR5s attenuated self-administration of cocaine and other addictive drugs in rats. How these animal findings extend to humans remains unclear. Therefore, we investigated if human cocaine users (CU) exhibit altered mGluR5 availability compared with drug-naïve control subjects. Seventeen male controls (11 smokers) and 18 male cocaine users (13 smokers) underwent positron emission tomography with (11)C-ABP688 to quantify mGluR5 availability in 12 volumes of interest in addiction-related brain areas. Drug use was assessed by self-report and quantitative hair toxicology. CU and controls did not significantly differ in regional mGluR5 availability. In contrast, smokers (n=24) showed significantly lower mGluR5 density throughout the brain (mean 20%) compared with non-smokers (n=11). In terms of effect sizes, lower mGluR5 availability was most pronounced in the caudate nucleus (d=1.50, 21%), insula (d=1.47, 20%), and putamen (d=1.46, 18%). Duration of smoking abstinence was positively associated with mGluR5 density in all brain regions of interest, indicating that lower mGluR5 availability was particularly pronounced in individuals who had smoked very recently. Specifically tobacco smoking was associated with lower mGluR5 availability in both CU and controls, while cocaine use was not linked to detectable mGluR5 alterations. These findings have important implications regarding the development of novel pharmacotherapies aimed at facilitating smoking cessation.Molecular Psychiatry advance online publication, 30 April 2013; doi:10.1038/mp.2013.51. HubMed – addiction


Adolescent drinking targets corticotropin releasing factor (CRF) peptide labeled cells in the central amygdala of male and female rats.

Neuroscience. 2013 Apr 26;
Karanikas CA, Lu YL, Richardson HN

Adolescence is a developmental period when many teenagers first drink alcohol and often engage in binge drinking. Early onset of alcohol is linked to increased risk of stress-related disorders in adulthood in humans, suggesting that alcohol may interfere with development of the stress regulatory system. We investigated the effect of voluntary alcohol exposure on corticotropin releasing factor (CRF) peptide producing cells in the central nucleus of the amygdala (CeA) in adolescent male and female rats. These cells are important for the autonomic and behavioral responses to stress, have been implicated in addiction, and change over adolescent development. Animals self-administered sweetened alcohol during early adolescence (postnatal days 28-42) and brains were obtained on postnatal day 43 for CRF peptide immunolabeling. Females had fewer CRF immunoreactive (-ir) cells in the CeA compared to males. In both males and females, alcohol self-administration reduced the number of CRF-ir cells in the CeA compared to control conditions in which rats self-administered equivalent levels of sweetened water that did not contain alcohol. Reduced peptide labeling was not observed in the bed nucleus of the stria terminalis (BNST), indicating regional specificity of these changes. Alterations within the CRF cell population of the amygdala may have important implications for susceptibility to alcohol and stress disorders during adolescence and later on in life. HubMed – addiction