Pharmacogenetics of Dopamine β‐Hydroxylase in cocaine dependence therapy with doxazosin
Abstract
The α1‐adrenergic antagonist, doxazosin, has improved cocaine use disorder (CUD) presumably by blocking norepinephrine (NE) stimulation and reward from cocaine‐induced NE increases. If the NE levels for release were lower, then doxazosin might more readily block this NE stimulation and be more effective. The NE available for release can be lower through a genetic polymorphism in dopamine β‐hydroxylase (DBH) (C‐1021T, rs1611115), which reduces DβH's conversion of dopamine to NE. We hypothesize that doxazosin would be more effective in CUD patients who have these genetically lower DβH levels. This 12‐w...
Source: Addiction Biology - March 2, 2018 Category: Addiction Authors: Xuefeng Zhang, David A. Nielsen, Coreen B. Domingo, Daryl I. Shorter, Ellen M. Nielsen, Thomas R. Kosten Tags: Original Article Source Type: research
Genome ‐wide association study in Finnish twins highlights the connection between nicotine addiction and neurotrophin signaling pathway
Abstract
The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome‐wide association study on 1715 ever smokers ascertained from the population‐based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence‐based Finnish reference panel. We analyzed three measures of nicotine addiction—smoking qu...
Source: Addiction Biology - March 1, 2018 Category: Addiction Authors: Jenni H ällfors, Teemu Palviainen, Ida Surakka, Richa Gupta, Jadwiga Buchwald, Anu Raevuori, Samuli Ripatti, Tellervo Korhonen, Pekka Jousilahti, Pamela A.F. Madden, Jaakko Kaprio, Anu Loukola Tags: Original Article Source Type: research
Evidence of subgroups in smokers as revealed in clinical measures and evaluated by neuroimaging data: a preliminary study
Abstract
To date, fractionation of the nicotine addiction phenotype has been limited to that based primarily on characteristics of cigarette use, although it is widely appreciated that a variety of individual factors are associated with tobacco use disorder. Identifying subtypes of tobacco use disorder based on such factors may lead to better understanding of potential treatment targets, individualize treatments and improve outcomes. In this preliminary study, to identify potential subgroups, we applied hierarchical clustering to a broad range of assessments measuring personality, IQ and psychiatric symptoms, as well as va...
Source: Addiction Biology - March 1, 2018 Category: Addiction Authors: Xiaoyu Ding, Betty Jo Salmeron, Jamei Wang, Yihong Yang, Elliot A. Stein, Thomas J. Ross Tags: Original Article Source Type: research
Enhanced neuronal and blunted hemodynamic reactivity to cocaine in the prefrontal cortex following extended cocaine access: optical imaging study in anesthetized rats
Abstract
Cocaine addiction is associated with dysfunction of the prefrontal cortex (PFC), which facilitates relapse and compulsive drug taking. To assess if cocaine's effects on both neuronal and vascular activity contribute to PFC dysfunction, we used optical coherence tomography and multi‐wavelength laser speckle to measure vascularization and hemodynamics and used GCaMP6f to monitor intracellular Ca2+ levels ([Ca2+]in) as a marker of neuronal activity. Rats were given short (1 hour; ShA) or long (6 hours; LgA) access cocaine self‐administration. As expected, LgA but not ShA rats escalated cocaine intake. In naïve...
Source: Addiction Biology - March 1, 2018 Category: Addiction Authors: Craig P. Allen, Kicheon Park, Ang Li, Nora D. Volkow, George F. Koob, Yingtian Pan, Xiu ‐Ti Hu, Congwu Du Tags: Original Article Source Type: research
Preclinical evidence for combining the 5 ‐HT2C receptor agonist lorcaserin and varenicline as a treatment for nicotine dependence
Abstract
Varenicline, a nicotinic acetylcholine receptor partial agonist, is used to treat nicotine dependence. Lorcaserin, a 5‐HT2C receptor agonist has been approved in some countries to treat obesity. Based on preclinical and preliminary clinical evidence, lorcaserin may have potential to treat nicotine dependence. These experiments examined in rats the effects of combining varenicline (0.5 or 1 mg/kg) and lorcaserin (0.3, 0.6 and 1 mg/kg) on nicotine self‐administration, reinstatement of nicotine seeking, responding for food and impulsive action. Both drugs alone reduced nicotine self‐administration. Combining ...
Source: Addiction Biology - March 1, 2018 Category: Addiction Authors: Paul J. Fletcher, Zhaoxia Li, Leo B. Silenieks, Cam MacMillan, Ines DeLannoy, Guy A. Higgins Tags: Original Article Source Type: research
The monoamine stabilizer ( −)‐OSU6162 prevents the alcohol deprivation effect and improves motor impulsive behavior in rats
In conclusion, our results provide further support for OSU6162 as a novel treatment for alcohol use disorder. The results further indicate that improvement of motor impulse control might be one mechanism behind OSU6162's ability to attenuate alcohol‐mediated behaviors.
A main problem in the treatment of alcohol use disorder (AUD) is the long‐lasting vulnerability to relapse. Impaired impulse control, often seen in AUD individuals, contribute to relapse to alcohol drinking. Here, we showed that the monoamine stabilizer OSU6162 improved motor impulsivity (i.e. decreased premature responses) in both alcohol‐naive and a...
Source: Addiction Biology - February 26, 2018 Category: Addiction Authors: Ida Fredriksson, Malin Wirf, Pia Steensland Tags: Original Article Source Type: research
The monoamine stabilizer ( −)‐OSU6162 prevents the alcohol deprivation effect and improves motor impulsive behavior in rats
Addiction Biology, EarlyView. (Source: Addiction Biology)
Source: Addiction Biology - February 26, 2018 Category: Addiction Source Type: research
Not all smokers appear to seek nicotine for the same reasons: implications for preclinical research in nicotine dependence
Addiction Biology, EarlyView. (Source: Addiction Biology)
Source: Addiction Biology - February 26, 2018 Category: Addiction Source Type: research
Lysophosphatidic acid ‐induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine‐contextual memory
Addiction Biology, EarlyView. (Source: Addiction Biology)
Source: Addiction Biology - February 26, 2018 Category: Addiction Source Type: research
Stress augments the rewarding memory of cocaine via the activation of brainstem ‐reward circuitry
Addiction Biology, EarlyView. (Source: Addiction Biology)
Source: Addiction Biology - February 26, 2018 Category: Addiction Source Type: research
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Addiction Biology, Ahead of Print. (Source: Addiction Biology)
Source: Addiction Biology - February 26, 2018 Category: Addiction Source Type: research
Stress augments the rewarding memory of cocaine via the activation of brainstem ‐reward circuitry
Abstract
Effects of stress on the reward system are well established in the literature. Although previous studies have revealed that stress can reinstate extinguished addictive behaviors related to cocaine, the effects of stress on the rewarding memory of cocaine are not fully understood. Here, we provide evidence that stress potentiates the expression of rewarding memory of cocaine via the activation of brainstem‐reward circuitry using a cocaine‐induced conditioned place preference (CPP) paradigm combined with restraint stress in rats. The rats exposed to 30‐minute restraint stress immediately before posttest exhibi...
Source: Addiction Biology - February 26, 2018 Category: Addiction Authors: Fumiya Shinohara, Yuta Asaoka, Hironori Kamii, Masabumi Minami, Katsuyuki Kaneda Tags: Original Article Source Type: research
