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Addiction Biology

Alexandra Chisholm, Jessica Iannuzzi, Damaris Rizzo, Natasha Gonzalez, Émilie Fortin, Alexandra Bumbu, Ariel A Batallán Burrowes, C Andrew Chapman, Uri Shalev
Drug addiction is a chronic disorder that is characterized by compulsive drug seeking and involves cycling between periods of compulsive drug use, abstinence, and relapse. In both human addicts and animal models of addiction, chronic food restriction has been shown to increase rates of relapse. Previously, our laboratory has demonstrated a robust increase in drug seeking following a period of withdrawal in chronically food-restricted rats compared with sated rats. To date, the neural mechanisms that mediate the effect of chronic food restriction on drug seeking have not been elucidated...
January 9, 2019: Addiction Biology
Yadi Li, Zaixu Cui, Qi Liao, Haibo Dong, Jianbing Zhang, Wenwen Shen, Wenhua Zhou
Arterial spin labeling (ASL) magnetic resonance imaging has been widely applied to identify cerebral blood flow (CBF) abnormalities in a number of brain disorders. To evaluate its significance in detecting methamphetamine (MA) dependence, this study used a multivariate pattern classification algorithm, ie, a support vector machine (SVM), to construct classifiers for discriminating MA-dependent subjects from normal controls. Forty-five MA-dependent subjects, 45 normal controls, and 36 heroin-dependent subjects were enrolled...
January 9, 2019: Addiction Biology
David Roura-Martínez, Marcos Ucha, Javier Orihuel, Inmaculada Ballesteros-Yáñez, Carlos Alberto Castillo, Alberto Marcos, Emilio Ambrosio, Alejandro Higuera-Matas
Relapse into drug use is a major problem faced by recovering addicts. In humans, an intensification of the desire for the drug induced by environmental cues-incubation of drug craving-has been observed. In rodents, this phenomenon has been modeled by studying drug seeking under extinction after different times of drug withdrawal (or using a natural reinforcer). Although much progress has been made, an integrated approach simultaneously studying different drug classes and natural reward and examining different brain regions is lacking...
January 8, 2019: Addiction Biology
Guangheng Dong, Min Wang, Xiaoyue Liu, Qianxin Liang, Xiaoxia Du, Marc N Potenza
Internet gaming disorder (IGD) is associated with negative health measures. However, little is known regarding the brain mechanisms or cognitive factors that may predict transitions from regular game use (RGU) to IGD. Such knowledge may help identify individuals who are particularly vulnerable to IGD and aid in prevention efforts. One hundred forty-nine individuals with RGU were scanned when they were performing a cue-elicited-craving task before gaming and after gaming was suddenly ceased. One year later, 23 were found to have developed IGD (RGU_IGD)...
January 6, 2019: Addiction Biology
Alena M Sentir, Richard L Bell, Eric A Engleman, R Andrew Chambers
Multiple addictions frequently occur in patients with mental illness. However, basic research on the brain-based linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35-60)...
December 28, 2018: Addiction Biology
Christian Montanari, Elodie Giorla, Yann Pelloux, Christelle Baunez
Drug intake is known to be under the influence of social context. We have recently shown that presence of a peer influences drug intake in both rats and humans. Whether or not social acoustic communications between the peers play a role during cocaine or sucrose self-administration (SA) was investigated here using playback of ultrasonic vocalizations (USVs) at 50 and 22 kHz, conveying, respectively, positive and negative internal affective states in adult rats. To assess the neurobiological substrate of a potential USV influence on drug and food intake, we tested the effects of subthalamic nucleus (STN) lesions, given its role in emotional and motivational processes...
December 28, 2018: Addiction Biology
Xin-Yu Fan, Jing-Yu Yang, Ying-Xu Dong, Ying Hou, Shuai Liu, Chun-Fu Wu
Methamphetamine (METH) causes memory changes, but the underlying mechanisms are poorly understood. Epigenetic mechanisms, including DNA methylation, can potentially cause synaptic changes in the brain. Oxytocin (OT) plays a central role in learning and memory, but little is known of the impact of OT on METH-associated memory changes. Here, we explored the role of OT in METH-induced epigenetic alterations that underlie spatial and cognitive memory changes. METH (2.0 mg/kg, i.p.) was administered to male C57BL/6 mice once every other day for 8 days...
December 25, 2018: Addiction Biology
Kirsten C Morley, Jim Lagopoulos, Warren Logge, Andrew Baillie, Claire Adams, Paul S Haber
BACKGROUND AND AIMS: Baclofen, a selective γ-aminobutyric acid (GABA)B receptor agonist, has emerged as a potential treatment for alcohol use disorder with much unexplained variation in response to treatment efficacy and dose regimen. Several positive studies include patients with alcoholic liver disease (ALD) and/or history of heavy drinking. The aim of this paper was to examine the association of cortical GABA+ concentration with severity of liver disease (including markers of liver injury) and other clinical characteristics in alcohol patients...
December 18, 2018: Addiction Biology
Witold X Chmielewski, Nicolas Zink, Keluf Ylva Chmielewski, Christian Beste, Ann-Kathrin Stock
Binge drinking is an increasingly prevalent pattern of alcohol consumption that impairs top-down cognitive control to a much stronger degree than automatic response generation. Even though an imbalance of those two antagonistic processes fosters the development and maintenance of alcohol use disorders (AUDs), it has never been directly investigated how binge drinking affects the interaction of those two processes. We therefore assessed a sample of n = 35 healthy young men who were asked to perform a newly developed Simon Nogo paradigm once sober and once intoxicated (~1...
December 18, 2018: Addiction Biology
Christian Sommer, Julian Birkenstock, Maria Garbusow, Elisabeth Obst, Daniel J Schad, Nadine Bernhardt, Quentin M Huys, Friedrich M Wurst, Wolfgang Weinmann, Andreas Heinz, Michael N Smolka, Ulrich S Zimmermann
We demonstrated that alcohol-dependent patients who relapsed within 1 year after detoxification showed stronger PIT effects compared with abstainers and controls. Relapsers particularly failed to correctly perform in trials where an instrumental stimulus required inhibition while a Pavlovian background cue indicated a monetary gain. Under that condition, relapsers approached the instrumental stimulus, independent of the expected punishment. The failure of inhibiting an aversive stimulus in favor of approaching an appetitive context cue reflects dysfunctional altered learning mechanisms in relapsers...
December 18, 2018: Addiction Biology
Danai Riga, Leanne J M Schmitz, Yvar van Mourik, Witte J G Hoogendijk, Taco J De Vries, August B Smit, Sabine Spijker
Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (five episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance...
December 18, 2018: Addiction Biology
Nadege Morisot, Anthony L Berger, Khanhky Phamluong, Alan Cross, Dorit Ron
Fyn is a member of the Src family of protein tyrosine kinases (PTKs) that plays an important role not only in normal synaptic functions but also in brain pathologies including alcohol use disorder. We previously reported that repeated cycles of binge drinking and withdrawal activate Fyn in the dorsomedial striatum (DMS) of rodents, and that Fyn signaling in the DMS contributes to rat alcohol intake and relapse. Here, we used AZD0530, a CNS penetrable inhibitor of Src PTKs developed for the treatment of Alzheimer disease and cancer and tested its efficacy to suppress alcohol-dependent molecular and behavioral effects...
December 7, 2018: Addiction Biology
Martin Fungisai Gerchen, Alena Rentsch, Martina Kirsch, Falk Kiefer, Peter Kirsch
Frontostriatal circuits are centrally involved in the selection of behavioral programs and play a prominent role in alcohol use disorder (AUD) as well as other mental disorders. However, how frontal regions change their striatal connectivity to implement adaptive cognitive control is still not fully understood. Here, we developed an approach for functional magnetic resonance imaging (fMRI) connectivity analysis in which we change the focus from connectivity to individual voxels towards spatial information about the location of strongest functional connectivity...
November 23, 2018: Addiction Biology
Sudarat Nimitvilai, Marcelo F Lopez, John J Woodward
Biological differences between males and females likely influence responses to alcohol and the propensity to engage in excessive drinking. In both humans and rodents, females escalate alcohol use and develop addiction-like behaviors faster than males, while males exhibit more severe withdrawal symptoms during abstinence. The mechanisms underlying these differences are not yet known but may reflect fundamental differences in the ethanol sensitivity of neurons in reward and control areas of the brain. To address this question, we recorded current-evoked spiking of lateral orbitofrontal cortex (lOFC) neurons in male and female C57BL/6J mice following acute and chronic exposure to ethanol...
November 23, 2018: Addiction Biology
Karen K Szumlinski, Alexis W Ary, Christina B Shin, Melissa G Wroten, Justin Courson, Bailey W Miller, Micaela Ruppert-Majer, John W Hiller, John R Shahin, Osnat Ben-Shahar, Tod E Kippin
Phosphatidylinositide 3-kinases (PI3Ks) are intracellular signal transducer enzymes that recruit protein kinase B (aka Akt) to the cell membrane, the subsequent activation of which regulates many cellular functions. PI3K/Akt activity is up-regulated within mesocorticolimbic structures in animal models of alcoholism, but less is known regarding PI3K/Akt activity in animal models of cocaine addiction. Given that prefrontal cortex (PFC) is grossly dysregulated in addiction, we studied how cocaine affects protein indices of PFC PI3K/Akt activity in rat and mouse models and examined the relevance of PI3K activity for cocaine-related learning...
November 18, 2018: Addiction Biology
Elena de Miguel, Olga Vekovischeva, Katja Kuokkanen, Marja Vesajoki, Nelli Paasikoski, Janne Kaskinoro, Mikko Myllymäki, Mira Lainiola, Sanna K Janhunen, Petri Hyytiä, Anni-Maija Linden, Esa R Korpi
Drugs of abuse induce widespread synaptic adaptations in the mesolimbic dopamine (DA) neurons. Such drug-induced neuroadaptations may constitute an initial cellular mechanism eventually leading to compulsive drug-seeking behavior. To evaluate the impact of GABAB receptors on addiction-related persistent neuroplasticity, we tested the ability of orthosteric agonist baclofen and two positive allosteric modulators (PAMs) of GABAB receptors to suppress neuroadaptations in the ventral tegmental area (VTA) and reward-related behaviors induced by ethanol and cocaine...
November 13, 2018: Addiction Biology
Stephanie E Wemm, Zhimin Cao, Liqiao Han, Edelgard Wulfert
Addictions, both substance and behavioral, have been conceptualized as involving similar biopsychosocial processes with different opportunistic expressions. A maladaptive stress response in combination with craving or urges to engage in the addictive behavior may be among the underlying factors common to behavioral and substance addictions. The current study compared the neuroendocrine (cortisol) and subjective responses to stress of gamblers and smokers to healthy controls. We assessed if participants responded differently to smoking or gambling cues before and after a psychosocial stressor...
November 13, 2018: Addiction Biology
Francisco J Pavón, Antonia Serrano, David G Stouffer, Ilham Polis, Marisa Roberto, Benjamin F Cravatt, Rémi Martin-Fardon, Fernando Rodríguez de Fonseca, Loren H Parsons
Deletion of fatty acid amide hydrolase (FAAH), enzyme responsible for degrading endocannabinoids, increases alcohol consumption and preference. However, there is a lack of data on neurochemical events in mice exposed to alcohol in the absence of FAAH. Extracellular levels of endocannabinoids and relevant neurotransmitters were measured by in vivo microdialysis in the nucleus accumbens (NAc) of FAAH knockout (KO) and wild-type (WT) mice during an ethanol (EtOH; 2 g/kg, ip) challenge in EtOH-naive and repeated (r) EtOH-treated mice...
November 13, 2018: Addiction Biology
Andrea L Gutman, Caitlin V Cosme, Maria F Noterman, Wensday R Worth, John A Wemmie, Ryan T LaLumiere
Acid-sensing ion channels (ASICs) are abundantly expressed in the nucleus accumbens core (NAcore), a region of the mesolimbocortical system that has an established role in regulating drug-seeking behavior. Previous work shows that a single dose of cocaine reduced the AMPA-to-NMDA ratio in Asic1a-/- mice, an effect observed after withdrawal in wild-type mice, whereas ASIC1A overexpression in the NAcore of rats decreases cocaine self-administration. However, whether ASIC1A overexpression in the NAcore alters measures of drug-seeking behavior after the self-administration period is unknown...
November 6, 2018: Addiction Biology
Giulia Donvito, Pretal P Muldoon, Kia J Jackson, Urslan Ahmad, Nur T Zaveri, J Michael McIntosh, Xiangning Chen, Aron H Lichtman, M Imad Damaj
Cessation from prolonged use of ∆9 -tetrahydrocannabinol (THC), the primary active compound responsible for the cannabimimetic effects of cannabis, results in a mild to moderate withdrawal syndrome in humans and laboratory animals. Whereas manipulations of the endogenous cannabinoid system (eg, cannabinoid receptors and endocannabinoid regulating enzymes) alter nicotine withdrawal, in this study we asked the reciprocal question. Do nicotinic acetylcholine receptors (nAChRs) modulate THC withdrawal? To assess the role of different nAChR subtypes in THC withdrawal, we used transgenic mouse, preclinical pharmacological, and human genetic correlation approaches...
October 31, 2018: Addiction Biology
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