Neural Correlates of Impulsivity in Healthy Males and Females With Family-Histories of Alcoholism.

Neural Correlates of Impulsivity in Healthy Males and Females with Family-Histories of Alcoholism.

Neuropsychopharmacology. 2013 Apr 12;
Devito EE, Meda SA, Jiantonio R, Potenza MN, Krystal JH, Pearlson GD

Individuals family-history positive for alcoholism (FHP) have increased risk for the disorder, which may be mediated by intermediate behavioral traits such as impulsivity. Given sex-differences in the risk for and clinical presentation of addictive disorders, risk for addiction may be differentially mediated by impulsivity within FHP males and females. FHP (N=28) and family-history negative (FHN, N=31) healthy, non-substance-abusing adults completed an fMRI Go/No-Go task and were assessed on impulsivity and alcohol use. Effects of family-history and sex were investigated as were associations between neural correlates of impulse-control and out-of-scanner measures of impulsivity and alcohol use. FHP individuals showed greater activation in the left anterior insula and inferior frontal gyrus during successful inhibitions, an effect that was driven primarily by FHP males. Higher self-reported impulsivity and behavioral discounting impulsivity, but not alcohol use measures, were associated with greater BOLD signal in the region that differentiated FHP and FHN groups. Impulsivity factors were associated with alcohol use measures across FHP and FHN groups. These findings are consistent with increased risk for addiction amongst FHP individuals being conferred through disrupted function within neural systems important for impulse-control.Neuropsychopharmacology accepted article preview online, 12 April 2013; doi:10.1038/npp.2013.92. HubMed – addiction


Participation in opioid substitution treatment reduces the rate of criminal convictions: Evidence from a community study.

Addict Behav. 2013 Mar 22; 38(7): 2313-2316
Vorma H, Sokero P, Aaltonen M, Turtiainen S, Hughes LA, Savolainen J

OBJECTIVE: Positive outcomes associated with opioid substitution treatment include reduced illicit opioid use and lower risk of HIV and other blood-borne infections. The effect on the reduction of criminal activity remains unclear. Our aim was to investigate the impact of treatment on criminal activity using conviction register data. METHOD: This observational retrospective study included all new patients (N=169) enrolled in an opioid substitution treatment program in the Helsinki University Central Hospital Clinic for Addiction Psychiatry between 2000 and 2005. Psychiatric and psychosocial services were provided as part of the program. Patient treatments were followed up for 18months. Data on criminal convictions were collected for approximately 3years before and after the start of treatment. RESULTS: Mean rates of convictions decreased significantly during treatment. The effects were similar for total convictions, drug convictions, and property crime convictions. Although the numbers of violence and drunk driving convictions were too small to be analysed separately, on a bivariate level there was no indication of reduction in these crime types. Patients with amphetamine co-dependence fared best. Sex, age, other co-dependences or psychiatric diagnoses, negative urine analyses during the treatment, and dropping out from treatment had little impact on the outcomes. CONCLUSIONS: Opioid substitution treatment seems to reduce criminal activity effectively. However, more information is needed to determine how treatment influences different types of criminality and which types of patients benefit most. HubMed – addiction


Addictive behaviors and addiction-prone personality traits: Associations with a dopamine multilocus genetic profile.

Addict Behav. 2013 Mar 6; 38(7): 2306-2312
Davis C, Loxton NJ

The purpose of this study was to examine reward-related genetic risk for addictive behaviors in a healthy community sample (n=217) of men and women. We tested a mediation model predicting that a quantitative multilocus genetic profile score – reflecting the additive effects of alleles known to confer relatively increased dopamine signaling in the ventral striatum – would relate positively to a composite measure of addictive behaviors, and that this association would be mediated by personality traits consistently associated with addiction disorders. Our model was strongly supported by the data, and accounted for 24% of the variance in addictive behaviors. These data suggest that brain reward processes tend to exert their influence on addiction risk by their role in the development of relatively stable personality traits associated with addictive behaviors. HubMed – addiction


Genetic deletion of the adenosine A2A receptor prevents nicotine-induced upregulation of ?7, but not ?4?2* nicotinic acetylcholine receptor binding in the brain.

Neuropharmacology. 2013 Apr 11;
Metaxas A, Al-Hasani R, Farshim P, Tubby K, Berwick A, Ledent C, Hourani S, Kitchen I, Bailey A

Considerable evidence indicates that adenosine A2A receptors (A2ARs) modulate cholinergic neurotransmission, nicotinic acetylcholine receptor (nAChR) function, and nicotine-induced behavioural effects. To explore the interaction between A2A and nAChRs, we examined if the complete genetic deletion of adenosine A2ARs in mice induces compensatory alterations in the binding of different nAChR subtypes, and whether the long-term effects of nicotine on nAChR regulation are altered in the absence of the A2AR gene. Quantitative autoradiography was used to measure cytisine-sensitive [(125)I]epibatidine and [(125)I]?-bungarotoxin binding to ?4?2* and ?7 nAChRs, respectively, in brain sections of drug-naïve (n=6) or nicotine treated (n=5-7), wild-type and adenosine A2AR knockout mice. Saline or nicotine (7.8 mg/kg/day; free-base weight) were administered to male CD1 mice via subcutaneous osmotic minipumps for a period of 14 days. Blood plasma levels of nicotine and cotinine were measured at the end of treatment. There were no compensatory developmental alterations in nAChR subtype distribution or density in drug-naïve A2AR knockout mice. In nicotine treated wild-type mice, both ?4?2* and ?7 nAChR binding sites were increased compared with saline treated controls. The genetic ablation of adenosine A2ARs prevented nicotine-induced upregulation of ?7 nAChRs, without affecting ?4?2* receptor upregulation. This selective effect was observed at plasma levels of nicotine that were within the range reported for smokers (10-50 ng ml(-1)). Our data highlight the involvement of adenosine A2ARs in the mechanisms of nicotine-induced ?7 nAChR upregulation, and identify A2ARs as novel pharmacological targets for modulating the long-term effects of nicotine on ?7 receptors. HubMed – addiction


A role of TARPs in the expression and plasticity of calcium-permeable AMPARs: evidence from cerebellar neurons and glia.

Neuropharmacology. 2013 Apr 11;
Bats C, Farrant M, Cull-Candy SG

The inclusion of GluA2 subunits has a profound impact on the channel properties of AMPA receptors (AMPARs), in particular rendering them impermeable to calcium. While GluA2-containing AMPARs are the most abundant in the central nervous system, GluA2-lacking calcium-permeable AMPARs are also expressed in wide variety of neurons and glia. Accumulating evidence suggests that the dynamic control of the GluA2 content of AMPARs plays a critical role in development, synaptic plasticity, and diverse neurological conditions ranging from ischemia-induced brain damage to drug addiction. It is thus important to understand the molecular mechanisms involved in regulating the balance of AMPAR subtypes, particularly the role of their co-assembled auxiliary subunits. The discovery of transmembrane AMPAR regulatory proteins (TARPs), initially within the cerebellum, has transformed the field of AMPAR research. It is now clear that these auxiliary subunits play a key role in multiple aspects of AMPAR trafficking and function in the brain. Yet, their precise role in AMPAR subtype-specific regulation has only recently received particular attention. Here we review recent findings on the differential regulation of calcium-permeable (CP-) and -impermeable (CI-) AMPARs in cerebellar neurons and glial cells, and discuss the critical involvement of TARPs in this process. HubMed – addiction



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