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Brain restoration addiction

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
Christian Lüscher, Pierre Pollak
In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders...
2016: Swiss Medical Weekly
Agnieszka Michalak, Grazyna Biała
The consequences of alcohol dependence concern serious health care, social and economic problems. The scope of many studies is to better understand mechanisms underlying alcohol addiction in order to work out new, more effective treatment strategies. Alcohol affects many neurotransmission systems within the brain. In general, acute alcohol enhances inhibitory transmission, up-regulating the GABAergic system and impairing glutamatergic function, therefore interfering the balance between excitatory and inhibitory synaptic inputs...
January 2016: Acta Poloniae Pharmaceutica
David Miller, Merlene Miller, Kenneth Blum, Rajendra D Badgaiyan, Marcelo Febo
There are approximately 14,500 clinics and programs in America that provide treatment for all types of addictive behaviors we call "Reward Deficiency Syndrome (RDS)". While most of these have good intentions to provide needed help to the victims of RDS, we propose herein that most of their efforts, especially during periods of aftercare, are not based on the existing scientific evidence. We use "aftercare" to refer to any form of program or therapy following primary treatment including 12-Step programs. Very few programs actually provide any evidenced-based treatment approaches during this most vulnerable period in recovery...
October 21, 2015: Journal of Reward Deficiency Syndrome
P Porcu, A M Barron, C A Frye, A A Walf, S-Y Yang, X-Y He, A L Morrow, G C Panzica, R C Melcangi
Neuroactive steroids are endogenous neuromodulators synthesised in the brain that rapidly alter neuronal excitability by binding to membrane receptors, in addition to the regulation of gene expression via intracellular steroid receptors. Neuroactive steroids induce potent anxiolytic, antidepressant, anticonvulsant, sedative, analgesic and amnesic effects, mainly through interaction with the GABAA receptor. They also exert neuroprotective, neurotrophic and antiapoptotic effects in several animal models of neurodegenerative diseases...
February 2016: Journal of Neuroendocrinology
B Boury-Jamot, A Carrard, J L Martin, O Halfon, P J Magistretti, B Boutrel
A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning...
August 2016: Molecular Psychiatry
Jamie Peters, Michael D Scofield, Shannon M Ghee, Jasper A Heinsbroek, Carmela M Reichel
Rats that have self-administered methamphetamine (meth) under long access, but not short access, conditions do not recognize novel objects. The perirhinal cortex is critical for novelty detection, and perirhinal metabotropic glutamate 5 receptors (mGlu5) are downregulated after long-access meth. The novel positive allosteric modulator (PAM) 1-(4-(2,4-difluorophenyl) piperazin-1-yl)-2-((4-fluorobenzyl)oxy)-ethanone, or DPFE, demonstrates improved solubility compared with other mGlu5 PAMs, thus allowing brain-site-specific pharmacological studies...
May 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Isabelle Boileau, Tina McCluskey, Junchao Tong, Yoshiaki Furukawa, Sylvain Houle, Stephen J Kish
We previously reported very low levels of dopamine in post-mortem striatum of chronic methamphetamine users, raising the possibility that restoration of normal dopamine levels could help in this addiction and perhaps prevent early relapse. To establish relevance of this finding to the living brain, we tested whether striatal [(11)C]-(+)-dihydrotetrabenazine binding, a vesicular monoamine transporter probe sensitive to changes in (stored) vesicular dopamine, is elevated in methamphetamine users. Chronic methamphetamine users underwent [(11)C]-(+)-dihydrotetrabenazine positron emission tomography scans during early (mean 2...
March 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Christian Lüscher, Vincent Pascoli, Meaghan Creed
Optogenetics has enabled the characterization of the neural circuits involved in brain diseases, such as addiction, depression or obsessive compulsive disorders. Recently, the technique has also been used to propose blueprints for novel treatments aiming at restoring circuit function through the reversal of specific forms of synaptic plasticity. Since optogenetic manipulations cannot be immediately translated to human use, we argue that an intermediate strategy could consist of emulating optogenetic protocols with deep brain stimulation (DBS)...
December 2015: Current Opinion in Neurobiology
Mirjana Carli, Chrysaugi Kostoula, Giuseppina Sacchetti, Pierangela Mainolfi, Alessia Anastasia, Claudia Villani, Roberto William Invernizzi
Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2(-/-) mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2(-/-) mice while the release of dopamine (DA) was not affected...
November 2015: Journal of Neurochemistry
Anna M W Taylor, Annie Castonguay, Atefeh Ghogha, Pia Vayssiere, Amynah A A Pradhan, Lihua Xue, Sadaf Mehrabani, Juli Wu, Pat Levitt, Mary C Olmstead, Yves De Koninck, Christopher J Evans, Catherine M Cahill
Opioid dependence is accompanied by neuroplastic changes in reward circuitry leading to a negative affective state contributing to addictive behaviors and risk of relapse. The current study presents a neuroimmune mechanism through which chronic opioids disrupt the ventral tegmental area (VTA) dopaminergic circuitry that contributes to impaired reward behavior. Opioid dependence was induced in rodents by treatment with escalating doses of morphine. Microglial activation was observed in the VTA following spontaneous withdrawal from chronic morphine treatment...
March 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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