Association of Abstinence-Induced Alterations in Working Memory Function and COMT Genotype in Smokers.

Association of abstinence-induced alterations in working memory function and COMT genotype in smokers.

Psychopharmacology (Berl). 2013 Jul 5;
Ashare RL, Valdez JN, Ruparel K, Albelda B, Hopson RD, Keefe JR, Loughead J, Lerman C

The common methionine (met) for valine (val) at codon 158 (val(158)met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers.We sought to replicate the association of the COMT val allele with abstinence-induced alterations in working memory-related activity in task-positive (executive control) and task-negative (default mode network) regions.Forty smokers (20 val/val and 20 met/met) performed an N-back task while undergoing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) on two separate occasions: following 72 h of confirmed abstinence and during smoking as usual. An independent sample of 48 smokers who completed the identical N-back task during fMRI in smoking vs. abstinence for another study was used as a validation sample.Contrary to expectations, genotype by session interactions on BOLD signal in executive control regions (dorsolateral prefrontal cortex and dorsal cingulate/medial prefrontal cortex) revealed significant abstinence-induced reductions in the met/met group, but not the val/val group. Results also revealed that val/val smokers may exhibit less suppression of activation in task-negative regions such as the posterior cingulate cortex during abstinence (vs. smoking). These patterns were confirmed in the validation sample and in the whole-brain analysis, though the regions differed from the a priori regions of interest (ROIs) (e.g., precuneus, insula).The COMT val(158)met polymorphism was associated with abstinence-related working memory deficits in two independent samples of smokers. However, inconsistencies compared to prior findings and across methods (ROI vs. whole-brain analysis) highlight the challenges inherent in reproducing results of imaging genetic studies in addiction. HubMed – addiction


Pain and suicidality: Insights from reward and addiction neuroscience.

Prog Neurobiol. 2013 Jul 1;
Elman I, Borsook D, Volkow ND

Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system’s role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostetic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other “reward deficiency syndromes” and a new proposal for “enhanced anti-reward syndromes”. We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. HubMed – addiction


Oxycodone-induced conditioned place preference and sensitization of locomotor activity in adolescent and adult mice.

Pharmacol Biochem Behav. 2013 Jul 1;
Niikura K, Ho A, Kreek MJ, Zhang Y

Nonmedical use of the prescription opioid oxycodone has become a major public health problem in the United States, with special concern for adolescents. Although adults and adolescents have different sensitivities for drugs, little is known about the rewarding effects of oxycodone in adolescents compared to adults, even in rodent models. Here, we investigate sensitivity to oxycodone by the conditioned place preference assay of conditioned reward, and effect on the locomotor activity in adolescent (4 weeks old) and adult (10 weeks old) C57BL/6J mice. Mice of both ages were trained with multiple doses of oxycodone (0, 0.3, 1, and 3 mg/kg) and showed conditioned preference in a dose-dependent manner. The adult mice developed conditioned preference to the lowest dose tested (0.3 mg/kg), but adolescent mice did not. Dose-dependent oxycodone-induced increases in locomotor activity were observed across the conditioning session. Interestingly, adolescent mice developed greater sensitization to the locomotor-activating effects of oxycodone than adult mice. Thus differences in sensitivity to oxycodone, such as the lower initial sensitivity for conditioned preference but greater locomotor sensitization in adolescent mice, may indicate contributing factors in oxycodone abuse and later addiction in human adolescents. HubMed – addiction