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Brain restoration addiction

Oona Lagström, Klara Danielsson, Bo Söderpalm, Mia Ericson, Louise Adermark
BACKGROUND: Addiction has been conceptualized as a shift from controlled recreational use towards compulsive and habitual drug-taking behavior. Although the brain reward system is vital for alcohol reward and reinforcement, other neuronal circuits may be involved in controlling long-term alcohol-seeking and drug-taking behaviors. The aim of this study was to outline alcohol-induced neuroplasticity in defined cortical and striatal sub-regions, previously implicated in Alcohol use disorder (AUD)...
March 12, 2019: Alcoholism, Clinical and Experimental Research
Dongjian Chen, Chao Huang, Zhuo Chen
Lycopene is an aliphatic hydrocarbon carotenoid extracted from plants like tomatoes, papayas, and watermelons. Previous studies have shown that lycopene can exert prophylactic and/or therapeutic effects in different disorders, such as heart failure and neoplasm via anti-oxidative, anti-inflammatory, and anti-proliferative activities. In the central nervous system (CNS), lycopene also has prophylactic and/or therapeutic effects in different type of disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), cerebral ischemia, epilepsy, and depression...
January 4, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Primavera A Spagnolo, Luis J Gómez Pérez, Alberto Terraneo, Luigi Gallimberti, Antonello Bonci
Gambling disorder (GD), currently considered a behavioral addiction, show substantial similarities with substance use disorders (SUDs) in terms of neurobiology and phenomenology. These similarities have been recognized in the DSM-5, although several relevant differences still exist in the diagnostic criteria, in particular, with regard to the role of cue- and stress- induced craving. Craving, recently included as a new criterion for SUDs diagnosis only, is a key construct also in the pathophysiology of GD. Furthermore, brain imaging studies indicate that similar alterations in cortico-limbic-striatal and prefrontal control circuits underlie the emergence of craving states in both disorders...
December 21, 2018: European Journal of Neuroscience
James M Kasper, Ashley E Smith, Jonathan D Hommel
Cocaine use disorder (CUD) is characterized by repeated cycles of drug seeking and drug taking. Currently, there are no available pharmacotherapies to treat CUD, partially due to a lack of a mechanistic understanding of cocaine-evoked alterations in the brain that drive drug-related behaviors. Repeated cocaine use alters expression of numerous genes in addiction-associated areas of the brain and these alterations are in part driven by inter-subject genetic variability. Recent findings have shown the neuropeptide neuromedin U (NMU) and its receptor NMU receptor 2 (NMUR2) decrease drug-related behaviors, but it is unknown if substances of abuse alter NMU or NMUR2 expression...
2018: Frontiers in Behavioral Neuroscience
Bokyeong Kim, Sehyoun Yoon, Ryuichi Nakajima, Hyo Jin Lee, Hee Jeong Lim, Yeon-Kyung Lee, June-Seek Choi, Bong-June Yoon, George J Augustine, Ja-Hyun Baik
Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice ( Drd2 -/- ) normalized their enhanced impulsivity...
November 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Farid Motlagh, Fatimah Ibrahim, Rusdi Rashid, Niusha Shafiabady, Tahereh Seghatoleslam, Hussain Habil
Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain electrical abnormalities among heroin addicts. This study aims to investigate the acute and short-term effects of methadone administration on the brain's electrophysiological properties before and after daily methadone intake over 10 weeks of treatment among heroin addicts...
November 2018: Psychopharmacology
Robert A Rifkin, Deborah Huyghe, Xiaofan Li, Manasa Parakala, Erin Aisenberg, Stephen J Moss, Paul A Slesinger
GABAB R-dependent activation of G protein-gated inwardly rectifying potassium channels (GIRK or KIR 3) provides a well-known source of inhibition in the brain, but the details on how this important inhibitory pathway affects neural circuits are lacking. We used sorting nexin 27 (SNX27), an endosomal adaptor protein that associates with GIRK2c and GIRK3 subunits, to probe the role of GIRK channels in reward circuits. A conditional knockout of SNX27 in both substantia nigra pars compacta and ventral tegmental area (VTA) dopamine neurons leads to markedly smaller GABAB R- and dopamine D2 R-activated GIRK currents, as well as to suprasensitivity to cocaine-induced locomotor sensitization...
October 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Panos Zanos, Helen Keyworth, Polymnia Georgiou, Ian Kitchen, Andreas Zimmer, Alexis Bailey
Nicotine dependence and schizophrenia are two mental health disorders with remarkably high comorbidity. Cigarette smoking is particularly prevalent among schizophrenic patients and it is hypothesized to comprise a form of self-medication for relieving cognitive deficits in these patients. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin in the modulation of drug addiction, as well as schizophrenia symptomology; however, the underlying mechanism remains unclear. Therefore, we sought to investigate the effects of chronic nicotine administration on oxytocin receptor (OTR) binding in the brain of a transgenic mouse model of schizophrenia that carries a bacterial artificial chromosome of the human G72/G30 locus (G72Tg)...
September 15, 2018: European Journal of Neuroscience
Marek Gryz, Małgorzata Lehner, Aleksandra Wisłowska-Stanek, Adam Płaźnik
Dopaminergic system activity in limbic structures (reward system) is related to motivational processes and adaptation to changing environmental conditions. Stress conditions can cause dopaminergic dysfunction, reduce motivational processes and induce compensatory drug use. The susceptibility to stress is characterized by individual variability. Psychostimulants such as cocaine, amphetamine and its derivatives act as positive reinforcers, affecting mood changes. Prolonged use of psychoactive substances can cause persistent plastic changes in the limbic system (disruption of neurogenesis, neurons atrophy), resulting in addictions or other forms of psychopathology like mood disorders...
June 30, 2018: Psychiatria Polska
Alexey Ostroumov, John A Dani
Behavioral adaptations occur through remodeling of brain circuits, as arising, for instance, from experience-dependent synaptic plasticity. Drugs of abuse and aversive stimuli, such as stress, act on the mesocorticolimbic system, dysregulating adaptive mechanisms and leading to a variety of aberrant behaviors associated with neuropsychiatric disorders. Until recently, research in the field has commonly focused on experience-dependent synaptic plasticity at excitatory synapses. However, there is growing evidence that synaptic plasticity within inhibitory circuits is an important contributor to maladaptive behaviors...
December 2018: Trends in Neurosciences
Thomas C Thannickal, Joshi John, Ling Shan, Dick F Swaab, Ming-Fung Wu, Lalini Ramanathan, Ronald McGregor, Keng-Tee Chew, Marcia Cornford, Akihiro Yamanaka, Ayumu Inutsuka, Rolf Fronczek, Gert Jan Lammers, Paul F Worley, Jerome M Siegel
The changes in brain function that perpetuate opiate addiction are unclear. In our studies of human narcolepsy, a disease caused by loss of immunohistochemically detected hypocretin (orexin) neurons, we encountered a control brain (from an apparently neurologically normal individual) with 50% more hypocretin neurons than other control human brains that we had studied. We discovered that this individual was a heroin addict. Studying five postmortem brains from heroin addicts, we report that the brain tissue had, on average, 54% more immunohistochemically detected neurons producing hypocretin than did control brains from neurologically normal subjects...
June 27, 2018: Science Translational Medicine
Bing Wang, Cun-Jin Su, Teng-Teng Liu, Yan Zhou, Yu Feng, Ya Huang, Xu Liu, Zhi-Hong Wang, Li-Hua Chen, Wei-Feng Luo, Tong Liu
Parkinson's disease (PD) is a common neurodegenerative disease characterized the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Brain endogenous morphine biosynthesis was reported to be impaired in PD patients and exogenous morphine attenuated 6-hydroxydopamine (6-OHDA)-induced cell death in vitro . However, the mechanisms underlying neuroprotection of morphine in PD are still unclear. In the present study, we investigated the neuroprotective effects of low-dose morphine in cellular and animal models of PD and the possible underlying mechanisms...
2018: Frontiers in Molecular Neuroscience
Youli Guo, Chaohua Luo, Genghong Tu, Chan Li, Yi Liu, Wei Liu, Ken Kin Lam Yung, Zhixian Mo
Background: Addiction to ketamine is becoming a serious public health issues, for which there exists no effective treatment. Rhynchophylline (Rhy) is an alkaloid extracted from certain Uncaria species that is well known for both its potent anti-addictive and neuroprotective properties. Increasing evidence supports the contributions of cAMP response element binding protein (CREB), nuclear receptor-related-1 (Nurr1), and brain-derived neurotrophic factor (BDNF) in modulating neural and behavioral plasticity which was induced by addictive drugs...
January 2018: Pharmacognosy Magazine
Andrzej T Slominski, Michal A Zmijewski, Przemyslaw M Plonka, Jerzy P Szaflarski, Ralf Paus
The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain and restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine, and immune systems, all acting in concert to control body homeostasis. Although UV energy has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis but also induces skin pathology (e...
May 1, 2018: Endocrinology
Marian T Sepulveda-Orengo, Kati L Healey, Ronald Kim, Alyson C Auriemma, Jennifer Rojas, Nicholas Woronoff, Rachel Hyppolite, Kathryn J Reissner
Adaptations in glutamate signaling within the brain's reward circuitry are observed following withdrawal from several abused drugs, including cocaine. These include changes in intrinsic cellular excitability, glutamate release, and glutamate uptake. Pharmacological or optogenetic reversal of these adaptations have been shown to reduce measures of cocaine craving and seeking, raising the hypothesis that regulation of glutamatergic signaling represents a viable target for the treatment of substance use disorders...
May 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Corina N A M van den Heuvel, Anna C Navis, Tessa de Bitter, Houshang Amiri, Kiek Verrijp, Arend Heerschap, Karen Rex, Isabelle Dussault, Sean Caenepeel, Angela Coxon, Paul N Span, Pieter Wesseling, Wiljan Hendriks, William P J Leenders
The receptor tyrosine kinase (RTK) MET represents a promising tumor target in a subset of glioblastomas. Most RTK inhibitors available in the clinic today, including those inhibiting MET, affect multiple targets simultaneously. Previously, it was demonstrated that treatment with cabozantinib (MET/VEGFR2/RET inhibitor) prolonged survival of mice carrying orthotopic patient-derived xenografts (PDX) of the MET-addicted glioblastoma model E98, yet did not prevent development of recurrent and cabozantinib-resistant tumors...
November 2017: Molecular Cancer Research: MCR
Gessynger Morais-Silva, Gabrielle Cunha Alves, Marcelo T Marin
Ethanol addiction is a serious public health problem that still needs more effective pharmacological treatment. A key factor in the development and maintenance of this disease is the advent of neuroadaptations in the mesocorticolimbic brain pathway upon chronic ethanol abuse. In general, these neuroadaptations are maladaptive and affect numerous neurotransmitter systems and intracellular molecules. One of these molecules is ΔFosB, a transcription factor that is altered after chronic drug use. Behavioural sensitization is a useful model for the study of the neuroadaptations related to addiction...
November 2016: Neuropharmacology
Bok Soon Go, Jieun Kim, Ju Hwan Yang, Eun Sang Choe
The endoplasmic reticulum (ER) is a subcellular organelle that ensures proper protein folding process. The ER stress is defined as cellular conditions that disturb the ER homeostasis, resulting in accumulation of unfolded and/or misfolded proteins in the lumen of the ER. The presence of these proteins within the ER activates the ER stress response, known as unfolded protein response (UPR), to restore normal functions of the ER. However, under the severe and/or prolonged ER stress, UPR initiates apoptotic cell death...
August 2017: Molecular Neurobiology
Rebecca McKetin, Olivia M Dean, Amanda L Baker, Greg Carter, Alyna Turner, Peter J Kelly, Michael Berk
Methamphetamine dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of methamphetamine dependence. N-acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N-acetylcysteine also has antioxidant properties that protect against methamphetamine-induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of methamphetamine...
March 2017: Drug and Alcohol Review
Alicia Rivera, Belén Gago, Diana Suárez-Boomgaard, Takashi Yoshitake, Ruth Roales-Buján, Alejandra Valderrama-Carvajal, Ainhoa Bilbao, José Medina-Luque, Zaida Díaz-Cabiale, Kathleen Van Craenenbroeck, Dasiel O Borroto-Escuela, Jan Kehr, Fernando Rodríguez de Fonseca, Luis Santín, Adelaida de la Calle, Kjell Fuxe
Morphine is one of the most effective drugs used for pain management, but it is also highly addictive. Morphine elicits acute and long-term adaptive changes at cellular and molecular level in the brain, which play a critical role in the development of tolerance, dependence and addiction. Previous studies indicated that the dopamine D4 receptor (D4 R) activation counteracts morphine-induced adaptive changes of the μ opioid receptor (MOR) signaling in the striosomes of the caudate putamen (CPu), as well as the induction of several Fos family transcription factors...
September 2017: Addiction Biology
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