Framing Nicotine Addiction as a “Disease of the Brain”: Social and Ethical Consequences.

Framing Nicotine Addiction as a “Disease of the Brain”: Social and Ethical Consequences.

Soc Sci Q. 2012 Dec 1; 92(5): 1363-1388
Dingel MJ, Karkazis K, Koenig BA

In this article, we seek to better understand how a genomic vision of addiction may influence drug prevention and treatment. Though social influences on substance use and abuse (e.g., peer and family influence, socioeconomic status) are well documented, biomedical intervention is becoming increasingly technoscientific in nature. We wish to elucidate how emphasizing biological influences on substance use may lead to a vision of addiction as a phenomenon isolated within our bodies and neurochemistry, not lived daily within a complex social web of relationships and a particular political economy, including the tobacco industry, which aggressively markets products known to cause harm.We explore the emerging view of addiction as a “disease of the brain” in open-ended interviews with 86 stakeholders from the fields of nicotine research and tobacco control. Interview data were analyzed using standard qualitative techniques.Most stakeholders hold a medicalized view of addiction. Though environmental variables are understood to be a primary cause of smoking initiation, the speed and strength with which addiction occurs is understood to be a largely biological process. Though stakeholders believe that an increased focus on addiction as a disease of the brain is not likely to lead to widespread unrealistic expectations for cessation therapies, they remain concerned that it may reinforce teenagers’ expectations that quitting is not difficult. Finally, stakeholder responses indicate that genetic and neuroscientific research is unlikely to increase or decrease stigmatization, but will be used by interest groups to buttress their existing views of the stigma associated with smoking.We argue that the main potential harms of focusing on biological etiology stem from a concept of addiction that is disassociated from social context. Focusing on genetic testing and brain scans may lead one to overemphasize pharmaceutical “magic bullet cures” and underemphasize, and underfund, more traditional therapies and public health prevention strategies that have proven to be effective. Genetic research on addiction may fundamentally change our conception of deviance and our identities, and may thus transform our susceptibility to substance use into something isolated in our biology, not embedded in a biosocial context. HubMed – addiction

Class I HDAC inhibition blocks cocaine-induced plasticity by targeted changes in histone methylation.

Nat Neurosci. 2013 Mar 10;
Kennedy PJ, Feng J, Robison AJ, Maze I, Badimon A, Mouzon E, Chaudhury D, Damez-Werno DM, Haggarty SJ, Han MH, Bassel-Duby R, Olson EN, Nestler EJ

Induction of histone acetylation in the nucleus accumbens (NAc), a key brain reward region, promotes cocaine-induced alterations in gene expression. Histone deacetylases (HDACs) tightly regulate the acetylation of histone tails, but little is known about the functional specificity of different HDAC isoforms in the development and maintenance of cocaine-induced plasticity, and previous studies of HDAC inhibitors report conflicting effects on cocaine-elicited behavioral adaptations. Here we demonstrate that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior, an effect mediated in part through a chromatin-mediated suppression of GABAA receptor subunit expression and inhibitory tone on NAc neurons. Our findings suggest a new mechanism by which prolonged and selective HDAC inhibition can alter behavioral and molecular adaptations to cocaine and inform the development of therapeutics for cocaine addiction. HubMed – addiction

Influence of the novel histamine H3 receptor antagonist ST1283 on voluntary alcohol consumption and ethanol-induced place preference in mice.

Psychopharmacology (Berl). 2013 Mar 9;
Bahi A, Sadek B, Schwed SJ, Walter M, Stark H

RATIONALE: Growing evidence supports a role for the central histaminergic system to have a modulatory influence on drug addiction in general and alcohol-use disorders in particular through histamine H3 receptors (H3R). OBJECTIVE: In the present study, the effects of systemic injection of the newly synthesized H3R antagonist ST1283 on ethanol (EtOH) voluntary intake and EtOH-conditioned reward in mice have been investigated. METHODS: Oral EtOH, saccharin, and quinine intake was assessed in a two-bottle choice paradigm using escalating concentrations of alcohol or tastant solutions. EtOH-induced place preference (CPP), EtOH-induced locomotor activity, and blood ethanol concentration (BEC) were also measured. RESULTS: Following administration of the H3R antagonist (2.5, 5, and 10 mg/kg, i.p.), there was a significant dose-dependent decrease in alcohol consumption and preference. Importantly, vehicle- and ST1283 (5 mg/kg)-treated mice showed similar consumption and preference to increasing concentration of both sweet and bitter tastes. More interestingly, systemic administration of ST1283 inhibited EtOH-CPP and EtOH-enhanced locomotion. This inhibition was blocked when mice were pretreated with the selective H3R agonist R-(alpha)-methyl-histamine (10 mg/kg). Finally, vehicle- and ST1283-treated mice had similar BECs. CONCLUSION: Our results show that ST1283 may decrease voluntary EtOH consumption and EtOH-CPP by altering its reinforcing effects, suggesting a novel role for histamine signaling in regulation of alcoholism. Lastly, the results add to the growing literature on H3R modulation in the pharmacotherapy of EtOH addiction. HubMed – addiction

Hyposensitivity to Gamma-aminobutyric Acid in the Ventral Tegmental Area during Alcohol Withdrawal: Reversal by Histone Deacetylase Inhibitors.

Neuropsychopharmacology. 2013 Mar 8;
Arora DS, Nimitvilai S, Teppen TL, McElvain MA, Sakharkar AJ, You C, Pandey SC, Brodie MS

Putative dopaminergic (pDAergic) ventral tegmental area (VTA) neurons play an important role in alcohol addiction. Acute ethanol increases the activity of pDAergic neurons, and withdrawal from repeated ethanol administration produces a decreased sensitivity of pDA VTA neurons to GABA. Recent studies show that behavioral changes induced by chronic alcohol are reversed by inhibitors of histone deacetylases (HDACs). Whether HDAC-induced histone modifications regulate changes in GABA sensitivity of VTA pDAergic neurons during withdrawal is unknown. Here, we investigated modulation of withdrawal-induced changes in GABA sensitivity of pDA VTA neurons by HDAC inhibitors and also measured the levels of HDAC2, histone (H3-K9) acetylation, and GABA-A?1 receptor subunit in VTA during ethanol withdrawal. Mice were injected intraperitoneally with either ethanol (3.5?g/kg) or saline twice daily for 3 weeks. In recordings from pDA VTA neurons in brain slices from ethanol-withdrawn mice, sensitivity to GABA (50-500??M) was reduced. In brain slices from ethanol-withdrawn mice incubated with the HDAC inhibitor SAHA (vorinostat) or trichostatin A (TSA) for two hours, the hyposensitivity of pDA VTA neurons to GABA was significantly attenuated. There was no effect of TSA or SAHA on GABA sensitivity of pDA VTA neurons from saline-treated mice. In addition, ethanol withdrawal was associated with an increase in levels of HDAC2 and a decrease in histone (H3-K9) acetylation and levels of GABA (A- ?1) R subunits in the VTA. Therefore, blockade of upregulation of HDAC2 by HDAC inhibitors normalizes GABA hyposensitivity of pDAergic neurons developed during withdrawal after chronic ethanol treatment, which suggests the possibility that inhibition of HDACs can reverse ethanol-induced neuroadaptational changes in reward circuitry.Neuropsychopharmacology accepted article preview online, 8 March 2013; doi:10.1038/npp.2013.65. HubMed – addiction

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