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Addiction Biology

Zebin Lin, Yuancheng Chen, Jiaolun Li, Zhiru Xu, Hao Wang, Junyi Lin, Xing Ye, Ziqin Zhao, Yiwen Shen, Yurong Zhang, Shuiqing Zheng, Yulan Rao
N-Ethylpentylone (NEP) is one of the most confiscated synthetic cathinones in the world. However, its pharmacology and pharmacokinetics remain largely unknown. In this study, the pharmacokentics of NEP in rat nucleus accumbens (NAc) was assessed via brain microdialysis after the intraperitoneal (ip) administration of NEP (20 or 50 mg/kg). The concentrations of dopamine (DA) and serotonin (5-HT) and their metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and 5-hydroxyindoleacetic acid (5-HIAA), were simultaneously monitored to elucidate the pharmacological effect of NEP...
April 15, 2019: Addiction Biology
Valentina Licheri, Daniel Eckernäs, Filip Bergquist, Mia Ericson, Louise Adermark
Nicotine is recognized as one of the most addictive drugs, which in part could be attributed to progressive neuroadaptations and rewiring of dorsal striatal circuits. Since motor-skill learning produces neuroplasticity in the same circuits, we postulate that rotarod training could be sufficient to block nicotine-induced rewiring and thereby prevent long-lasting impairments of neuronal functioning. To test this hypothesis, Wistar rats were subjected to 15 days of treatment with either nicotine (0.36 mg/kg) or vehicle...
April 10, 2019: Addiction Biology
Brennon R Luster, Elizabeth S Cogan, Karl T Schmidt, Dipanwita Pati, Melanie M Pina, Kedar Dange, Zoé A McElligott
The United States is experiencing an opioid crisis imposing enormous fiscal and societal costs and driving the staggering overdose death rate. While prescription opioid analgesics are essential for treating acute pain, cessation of use in individuals with a physical dependence induces an aversive withdrawal syndrome that promotes continued drug use to alleviate/avoid these symptoms. Additionally, repeated bouts of withdrawal often lead to an increased propensity for relapse. Understanding the neurobiology underlying withdrawal is essential for providing novel treatment options to alleviate physiological and affective components accompanying the cessation of opiate use...
April 9, 2019: Addiction Biology
Benjamin Rolland, Laurence Dricot, Coralie Creupelandt, Pierre Maurage, Philippe De Timary
Numerous studies have explored the morphological differences of the brain between subjects with alcohol use disorder (AUD) and control subjects, but very few have investigated the impact of the duration of alcohol use disorder (DAD) and current level of alcohol consumption (CAC) within AUD subjects using magnetic resonance imaging (MRI). We compared the morphological MRI of 44 controls and 66 AUD subjects, recruited at the end of a detoxification program. Additional analyses within the AUD group determined which specific alterations were respectively associated with DAD and CAC using: (1) Bonferroni-corrected multivariable linear regressions to explore the DAD/CAC impact on brain volumes and (2) a general linear model (GLM module of FreeSurfer's Qdec) and Monte Carlo simulation to correct for multiple comparisons (P < 0...
April 9, 2019: Addiction Biology
Liam J Nestor, Brendan Behan, John Suckling, Hugh Garavan
Adolescence may be a period of increased vulnerability to the onset of drug misuse and addiction due to changes in developing brain networks that support cognitive and reward processing. Cannabis is a widely misused illicit drug in adolescence which can lead to dependence and alterations in reward-related neural functioning. Concerns exist that cannabis-related alterations in these reward networks in adolescence may sensitize behaviour towards all forms of reward that increase the risk of further drug use. Taking a functional connectomics approach, we compared an acutely abstinent adolescent cannabis-dependent (CAN) group with adolescent controls (CON) on global measures of network topology associated with anticipation on a monetary incentive delay task...
April 8, 2019: Addiction Biology
Meriem Haddar, Kyosuke Uno, Katsunori Azuma, Shin-Ichi Muramatsu, Atsumi Nitta
Shati/Nat8l is a novel N-acetyltransferase identified in the brain of mice treated with methamphetamine (METH). Shati/Nat8l mRNA is expressed in various brain areas, including the prefrontal cortex (PFC), where the expression level is higher than that in other brain regions. Shati/Nat8l overexpression in the nucleus accumbens (NAc) attenuates the pharmacological response to METH via mGluR3. Meanwhile, dopamine (DA) and glutamate dysregulations have been reported in the medial prefrontal cortex (mPFC) and NAc after METH self-administration and during reinstatement...
April 5, 2019: Addiction Biology
Jian-Jun Zhang, Feng-Ze Jiang, Wei Zheng, Ying Duan, Shu-Bo Jin, Fang Shen, Jing Liang, Ming Li, Nan Sui
Drug-reinforced excessive operant responding is one fundamental feature of long-lasting addiction-like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug-specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self-administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up-regulated after 1- and 7-day morphine SA (0...
April 5, 2019: Addiction Biology
Patrick A McConnell, Eric L Garland, Jon-Kar Zubieta, Roger Newman-Norlund, Shannon Powers, Brett Froeliger
Preclinical studies have shown effects of chronic exposure to addictive drugs on glutamatergic-mediated neuroplasticity in frontostriatal circuitry. These initial findings have been paralleled by human functional magnetic resonance imaging (fMRI) research demonstrating weaker frontostriatal resting-state functional connectivity (rsFC) among individuals with psychostimulant use disorders. However, there is a dearth of human imaging literature describing associations between long-term prescription opioid use, frontostriatal rsFC, and brain morphology among chronic pain patients...
April 4, 2019: Addiction Biology
Cathrin Rohleder, Franziska Pahlisch, Rudolf Graf, Heike Endepols, F Markus Leweke
Based on the contribution of the endocannabinoid system to the pathophysiology of schizophrenia, the primary pro-psychotic ingredient of Cannabis sativa, Δ-9-tetrahydrocannabinol (Δ-9-THC), is used in preclinical as well as clinical research to mimic schizophrenia-like symptoms. While it is common to administer lipid-based formulations of Δ-9-THC in human studies orally, intraperitoneal injections of water-based solutions are used in animal models. Because of the poor water solubility of Δ-9-THC, solubilizers such as ethanol and/or emulsifiers are needed for these preparations...
April 2, 2019: Addiction Biology
Qingyu Zhao, Adolf Pfefferbaum, Simon Podhajsky, Kilian M Pohl, Edith V Sullivan
The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15 years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1-weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248 d) and 128 age- and sex-matched control participants; subsets of these participants completed motor testing...
April 1, 2019: Addiction Biology
Laura O'Halloran, Laura M Rueda-Delgado, Lee Jollans, Zhipeng Cao, Rory Boyle, Christina Vaughan, Phillip Coey, Robert Whelan
Impulsivity is a multidimensional construct that is related to different aspects of alcohol use, abuse, and dependence. Inhibitory control, one facet of impulsivity, can be assayed using the stop-signal task (SST) and quantified behaviorally via the stop-signal reaction time (SSRT) and electrophysiologically using event-related potentials (ERPs). Research on the relationship between alcohol use and SSRTs, and between alcohol use and inhibitory-control ERPs, is mixed. Here, adult alcohol users (n = 79), with a wide range of scores on the Alcohol Use Disorders Identification Test (AUDIT), completed the SST under electroencephalography (EEG) (70% of participants had AUDIT total scores greater than or equal to 8)...
March 27, 2019: Addiction Biology
Giulia Scuppa, Stefano Tambalo, Simone Pfarr, Wolfgang H Sommer, Angelo Bifone
A few studies have reported aberrant functional connectivity in alcoholic patients, but the specific neural circuits involved remain unknown. Moreover, it is unclear whether these alterations can be reversed upon treatment. Here, we used functional MRI to study resting state connectivity in rats following chronic intermittent exposure to ethanol. Further, we evaluated the effects of SB-277011-a, a selective dopamine D3 receptor antagonist, known to decrease ethanol consumption. Alcohol-dependent and control rats (N = 13/14 per group), 3 weeks into abstinence, were administered SB-277011-a or vehicle before fMRI sessions...
March 24, 2019: Addiction Biology
Andreas Heinz, Laura S Daedelow, Carolin Wackerhagen, Gaetano Di Chiara
With the development of the ICD-11, the debate about classifying certain psychoactive substances such as antidepressant medication and caffeine as drugs of dependence is ignited again. We argue that any coherent theory of addiction needs to identify the neurobiological processes elicited by a potentially addictive substance and to clearly define the clinical symptoms associated with these processes, which can then be used to guide diagnosis. Tolerance development and withdrawal symptoms can occur with any pharmacologically active agent, and their presence is not a sufficient criterion for the clinical diagnosis of an addictive disorder...
March 21, 2019: Addiction Biology
Caroline B Pantazis, Gary Aston-Jones
The lateral septum (LS) is a brain region implicated in motivation, addiction, anxiety, and affect. We recently found that LS is necessary for cocaine-seeking behaviors including conditioned place preference and reinstatement of extinguished drug seeking, which involve LS input to limbic regions including ventral tegmental area (VTA) and orexin neurons in hypothalamus. Here, we microinjected baclofen-muscimol (B-M) in LS prior to testing in a behavioral economics (BE) paradigm. We found that intra-LS B-M decreased motivation (increased demand elasticity; α) for cocaine, but did not change consumption at low effort (Q0 )...
March 21, 2019: Addiction Biology
Cindy L Ehlers, Evie Phillips, Derek Wills, Jessica Benedict, Manuel Sanchez-Alavez
Alcohol exposure typically begins in adolescence, and frequent binge drinking has been associated with health risk behaviors including alcohol use disorders (AUDs). Few studies have documented the effects of a history of adolescent binge drinking on neurophysiological consequences in young adulthood. Synchrony of phase (phase locking (PL)) of event-related oscillations (EROs) within and between different brain areas reflects communication exchange between neural networks and is a sensitive measure of adolescent development in both rats and humans, and thus may be a good translational measure of the potential harmful effects of alcohol exposure during adolescence...
March 18, 2019: Addiction Biology
Braulio Muñoz, Scarlet Gallegos, Christian Peters, Pablo Murath, David M Lovinger, Gregg E Homanics, Luis G Aguayo
Here, we used knock-in (KI) mice that have ethanol-insensitive alpha 1 glycine receptors (GlyRs) (KK385/386AA) to examine how alpha 1 GlyRs might affect binge drinking and conditioned place preference. Data show that tonic alpha 1 GlyR-mediated currents were exclusively sensitive to ethanol only in wild-type mice. Behavioral studies showed that the KI mice have a higher intake of ethanol upon first exposure to drinking and greater conditioned place preference to ethanol. This study suggests that nonsynaptic alpha 1-containing GlyRs have a role in motivational and early reinforcing effects of ethanol...
March 18, 2019: Addiction Biology
Paul John Cocker, Jean-Yves Rotge, Marie-Laure Daniel, Aude Belin-Rauscent, David Belin
Impairments in cost-benefit decision making represent a cardinal feature of drug addiction. However, whether these alterations predate drug exposure, thereby contributing to facilitating loss of control over drug intake, or alternatively arise as a result of drug use and subsequently confer vulnerability to relapse has yet to be determined. Male Sprague-Dawley rats were trained to self-administer (SA) cocaine during 19 daily long-access (12-h) sessions; conditions reliably shown to promote escalation. One week after cocaine SA, rats underwent an extinction/relapse test immediately followed by conditioned stimuli-, stress-, and drug-primed reinstatement challenges...
March 7, 2019: Addiction Biology
Matthew E Sloan, Joshua L Gowin, Roshni Janakiraman, Corbin D Ester, Joel Stoddard, Bethany Stangl, Vijay A Ramchandani
Alcohol consumption is often assessed over weeks to months, but few attempts have been made to characterize alcohol consumption rates at the level of an individual drinking session. Here, we aimed to compare the rate of alcohol consumption in social drinkers at high risk for alcohol use disorder (AUD) and heavy drinkers. One hundred and sixty social drinkers and 48 heavy drinkers participated in an alcohol self-administration study. Social drinkers were classified as low risk or high risk for AUD based on sex, impulsivity, and family history of alcoholism...
March 1, 2019: Addiction Biology
Yang Zhang, Yan Sun, Zhoulong Yu, Yankun Sun, Xiangwen Chang, Lin Lu, Suhua Chang, Jie Shi
Methamphetamine (MA)-related psychiatric symptoms (MAP) are serious comorbidities of MA use and result in many social problems such as violence and suicide. We investigated the sociodemographic and genetic risk factors for persistent MAP of MA users (MUs) and constructed an early MAP prediction model. Derivation and replication samples had 1734 and 905 MUs, respectively. Symptom Checklist 90, Childhood Trauma Questionnaire, Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale-IV, and Social Support Rating Scale were used to assess the past-year prevalence of general MAP and life events retrospectively...
February 28, 2019: Addiction Biology
Ahmed El-Boraie, Taraneh Taghavi, Meghan J Chenoweth, Koya Fukunaga, Taisei Mushiroda, Michiaki Kubo, Caryn Lerman, Nicole L Nollen, Neal L Benowitz, Rachel F Tyndale
The nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is an index of CYP2A6 activity. CYP2A6 is responsible for nicotine's metabolic inactivation and variation in the NMR/CYP2A6 is associated with several smoking behaviors. Our aim was to integrate established alleles and novel genome-wide association studies (GWAS) signals to create a weighted genetic risk score (wGRS) for the CYP2A6 gene for European-ancestry populations. The wGRS was compared with a previous CYP2A6 gene scoring approach designed for an alternative phenotype (C2/N2; cotinine-d2/(nicotine-d2 + cotinine-d2))...
February 27, 2019: Addiction Biology
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