Brain Nitric Oxide Metabolites in Rats Preselected for Nicotine Preference and Intake.

Brain Nitric Oxide Metabolites in Rats Preselected for Nicotine Preference and Intake.

Neurosci Lett. 2013 Apr 30;
Keser A, Nesil T, Kanit L, Pogun S

Nicotine addiction is a serious health problem resulting in millions of preventable deaths worldwide. The gas messenger molecule nitric oxide (NO) plays a critical role in addiction, and nicotine increases nitric oxide metabolites (NOx) in the brain. Understanding the factors which underlie individual differences in nicotine preference and intake is important for developing effective therapeutic strategies for smoking cessation. The present study aimed to assess NO activity, by measuring its stable metabolites, in three brain regions that express high levels of nicotinic acetylcholine receptors in rats preselected for nicotine preference. Rats (n=88) were exposed to two-bottle, free choice of oral nicotine/water starting either as adolescents or adults; control animals received only water under identical conditions. Following 12 or six weeks of exposure, levels of NOx (nitrite+nitrate), were determined in the hippocampus, frontal cortex, and amygdala. Since the rats were singly housed during oral nicotine treatment, naïve rats were also included in the study to evaluate the effect of isolation stress. Isolation stress increased NOx in the hippocampus. Nicotine preference did not have a significant effect on NO activity, but rats with adolescent exposure had higher NOx levels in the frontal cortex compared to adult-onset rats. Our findings suggest that nicotine exposure during adolescence, regardless of the amount of nicotine consumed, results in higher NO activity in the frontal cortex of rats, which persists through adulthood. HubMed – addiction


Dopamine D3 Receptor Inactivation Attenuates Cocaine-Induced Conditioned Place Preference in Mice.

Neuropharmacology. 2013 May 2;
Song R, Zhang HY, Peng XQ, Su RB, Yang RF, Li J, Xi ZX, Gardner EL

The dopamine (DA) D3 receptor (D3R) has received much attention in medication development for treatment of addiction. However, the functional role of the D3R in drug reward and addiction has been a matter of debate. We recently reported that D3 receptor-knockout (D3(-/-)) mice display increased vulnerability to cocaine self-administration, which we interpret as a compensatory response to attenuated cocaine reward after D3R deletion. Here we report that D3(-/-) mice displayed attenuated cocaine-induced conditioned place response (CPP) compared to wild-type mice. Similarly, blockade of brain D3Rs by YQA-14, a novel DA D3 receptor antagonist, significantly and dose-dependently inhibits acquisition and expression of cocaine-induced CPP in WT mice, but not in D3(-/-) mice. These findings suggest that: 1) D3Rs play an important role in mediating cocaine’s rewarding effects; and 2) YQA-14 is a highly potent and selective D3R antagonist in vivo, which deserves further study as a candidate for treatment of cocaine addiction. HubMed – addiction


Epigenetic Mechanisms of Drug Addiction.

Neuropharmacology. 2013 Apr 30;
Nestler EJ

Drug addiction involves potentially life-long behavioral abnormalities that are caused in vulnerable individuals by repeated exposure to a drug of abuse. The persistence of these behavioral changes suggests that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype. Work over the past decade has demonstrated a crucial role for epigenetic mechanisms in driving lasting changes in gene expression in diverse tissues, including brain. This has prompted recent research aimed at characterizing the influence of epigenetic regulatory events in mediating the lasting effects of drugs of abuse on the brain in animal models of drug addiction. This review provides a progress report of this still early work in the field. As will be seen, there is robust evidence that repeated exposure to drugs of abuse induces changes within the brain’s reward regions in three major modes of epigenetic regulation-histone modifications such as acetylation and methylation, DNA methylation, and non-coding RNAs. In several instances, it has been possible to demonstrate directly the contribution of such epigenetic changes to addiction-related behavioral abnormalities. Studies of epigenetic mechanisms of addiction are also providing an unprecedented view of the range of genes and non-genic regions that are affected by repeated drug exposure and the precise molecular basis of that regulation. Work is now needed to validate key aspects of this work in human addiction and evaluate the possibility of mining this information to develop new diagnostic tests and more effective treatments for addiction syndromes. HubMed – addiction


Sleep and daytime function in adults with attention-deficit/hyperactivity disorder: subtype differences.

Sleep Med. 2013 May 2;
Yoon SY, Jain UR, Shapiro CM

OBJECTIVES: Although sleep disorders have been reported to affect more than half of adults with attention-deficit/hyperactivity disorder (ADHD), the association between sleep and ADHD is poorly understood. The aims of our study were to investigate sleep-related variables in adults with ADHD and to assess if any differences exist between ADHD of the predominantly inattentive (ADHD-I) and combined (ADHD-C) subtypes. METHODS: We used the Epworth sleepiness scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and the fatigue severity scale (FSS) to collect data on daytime sleepiness, sleep quality, and fatigue in 126 subjects (45 ADHD-I and 81 ADHD-C subjects). RESULTS: Approximately 85% of subjects reported excessive daytime sleepiness or poor sleep quality. The most common sleep concerns were initial insomnia, interrupted sleep, and feeling too hot. When examining ADHD subtype differences, ADHD-I subtypes reported poorer sleep quality and more fatigue than ADHD-C subtypes. Partial correlation analyses revealed that interrelationships between sleep quality, daytime sleepiness, and fatigue differ between ADHD subtypes; in ADHD-I subtypes fatigue was associated with sleep quality, while in the ADHD-C subtypes fatigue was associated with both sleep quality and daytime sleepiness. There also appears to be a subtype×gender interaction that affects the perception of fatigue, as subjective fatigue was markedly higher in ADHD-I women than in ADHD-C women. CONCLUSION: Altogether our data indicate that the interplay of variables associated with daytime function and sleep varies between ADHD subtypes. This finding may have considerable relevance in the management and pathophysiologic understanding of ADHD, and thus lead to tailored treatments for ADHD subtypes. HubMed – addiction


The Late Positive Potential (LPP) in Response to Varying Types of Emotional and Cigarette Stimuli in Smokers: A Content Comparison.

Int J Psychophysiol. 2013 May 2;
Minnix JA, Versace F, Robinson JD, Lam CY, Engelmann JM, Cui Y, Brown VL, Cinciripini PM

Identifying neural mechanisms associated with addiction has substantially improved the overall understanding of addictive processes. Indeed, research suggests that drug-associated cues may take advantage of neural mechanisms originally intended for emotional processing of stimuli relevant to survival. In this study, we investigated cortical responses to several categories of emotional cues (erotic, romance, pleasant objects, mutilation, sadness, unpleasant objects) as well as two types of smoking-related cues (people smoking and cigarette-related objects). We recorded ERPs from 180 smokers prior to their participation in a smoking cessation clinical trial and assessed emotional salience by measuring the amplitude of the late positive potential (LPP; 400 to 600 ms after picture onset). As expected, emotional and cigarette-related pictures prompted a significantly larger LPP than neutral pictures. The amplitude of the LPP increased as a function of picture arousal level, with high-arousing erotic and mutilation pictures showing the largest response in contrast to low-arousing pleasant and unpleasant objects, which showed the smallest response (other than neutral). Compared to females, male participants showed larger LPPs for high-arousing erotic and mutilation pictures. However, unlike emotional pictures, no difference was noted for the LPP between cigarette stimuli containing people versus those containing only objects, suggesting that in contrast to emotional objects, cigarette-related objects are highly relevant for smokers. We also compared the smokers to a small (N=40), convenience sample of never-smokers. We found that never-smokers had significantly smaller LPPs in response to erotic and cigarette stimuli containing only objects compared to smokers. HubMed – addiction



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