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Meth addiction

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https://www.readbyqxmd.com/read/29217282/atypical-dopamine-transporter-inhibitors-attenuate-compulsive-like-methamphetamine-self-administration-in-rats
#1
Brendan J Tunstall, Chelsea P Ho, Jianjing Cao, Janaína C M Vendruscolo, Brooke E Schmeichel, Rachel D Slack, Gianluigi Tanda, Alexandra J Gadiano, Rana Rais, Barbara S Slusher, George F Koob, Amy H Newman, Leandro F Vendruscolo
Methamphetamine (METH) is a highly addictive drug, but no pharmacological treatment is yet available for METH use disorders. Similar to METH, the wake-promoting drug (R)-modafinil (R-MOD) binds to the dopamine transporter (DAT). Unlike METH, R-MOD is not a substrate for transport by DAT and has low abuse potential. We tested the hypothesis that the atypical DAT inhibitor R-MOD and compounds that are derived from Modafinil would decrease METH intake by reducing the actions of METH at the DAT. We tested the effects of systemic injections of R-MOD and four novel Modafinil-derived ligands with increased DAT affinity (JJC8-016, JJC8-088, JJC8-089, and JJC8-091) on intravenous (i...
December 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29185481/methamphetamine-induces-dopamine-release-in-the-nucleus-accumbens-through-a-sigma-receptor-mediated-pathway
#2
David M Hedges, J Daniel Obray, Jordan T Yorgason, Eun Young Jang, Vajira K Weerasekara, Joachim D Uys, Frederick P Bellinger, Scott C Steffensen
Methamphetamine (METH) is a drug with a high addictive potential that is widely abused across the world. While it is known that METH dysregulates both dopamine transmission and dopamine reuptake, the specific mechanism of action remains obscure. One promising target of METH is the sigma receptor, a chaperone protein located on the membrane of the endoplasmic reticulum. Using fast-scan cyclic voltammetry, we show that METH-enhancement of evoked dopamine release and basal efflux is dependent on sigma receptor activation...
November 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29175029/depletion-of-d3-dopamine-receptor-affects-methamphetamine-induced-expression-patterns-of-pde4b-and-atf3
#3
Yanjiong Chen, Cuo Yang, Li Zhu, Jiaqi Li, Fanglin Guan, Teng Chen
The role of the D3 dopamine receptor (D3R) and the specific molecular mechanisms underlying the regulation of D3R via the cAMP signaling pathway in methamphetamine (METH) addiction are still unclear. Here, we measured changes in Pde4b and Atf3 in the cAMP signaling pathway of dopaminergic system components, including the nucleus accumbens (NAc), caudate putamen (CPu) and hippocampus (Hip), in D3R knockout mice(D3R-/-) 1h and 24h after METH-induced behavioral sensitization. We found that knocking out D3R attenuated METH-induced behavioral sensitization, and Pde4b and Atf3 exhibited different expression patterns in brain regions in response to METH...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29174638/upregulation-of-ccl7-and-ccl2-in-reward-system-mediated-through-dopamine-d1-receptor-signaling-underlies-methamphetamine-induced-place-preference-in-mice
#4
Fumihiro Saika, Norikazu Kiguchi, Naoki Wakida, Daichi Kobayashi, Yohji Fukazawa, Shinsuke Matsuzaki, Shiroh Kishioka
We previously showed that the CC-chemokine ligand 2 (CCL2)-CC-chemokine receptor 2 (CCR2) system is responsible for conditioned place preference (CPP) by methamphetamine (Meth). In this study, we investigated the roles for other chemokines mediating Meth-induced CPP and the upstream factors upregulating chemokines in mice. We found that CCL7 mRNA level was upregulated in the prefrontal cortex (PFC) after Meth administration (3mg/kg, subcutaneous), and increased CCL7 immunoreactivity was localized to the PFC NeuN-positive neurons...
November 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29165617/selective-activation-of-striatal-ngf-trka-p75ntr-mapk-intracellular-signaling-in-rats-that-show-suppression-of-methamphetamine-intake-30-days-following-drug-abstinence
#5
Oscar V Torres, Subramanian Jayanthi, Michael T McCoy, Jean Lud Cadet
Background: The continuing epidemic of methamphetamine (METH) addiction has prompted research aimed at understanding striatal dysfunctions potentially associated with long-term METH use. Methods: Here, we investigated transcriptional and translational alterations in the expression of neurotrophic factors in the rat striatum at 30 days following METH SA and footshock punishment. Male Sprague-Dawley rats were trained to self-administer METH (0.1 mg/kg/injection, i...
November 20, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29128447/developmental-perspectives-on-methamphetamine-abuse-exploring-adolescent-vulnerabilities-on-brain-and-behavior
#6
REVIEW
Sophia J Luikinga, Jee Hyun Kim, Christina J Perry
Most people that experience illicit drugs do so for the first time during adolescence, and methamphetamine (meth) is no exception. Therefore, research into the effects of meth should highlight the adolescent period. Despite this, the vast majority of current literature has mainly focused on meth exposure during adulthood. In this review, we first describe existing literature that compares the behavioral effects of meth where exposure occurs in adolescence compared to adulthood. Given that there are actually very few such studies, we also look at what is known about neural effects of meth in the adult brain, and relate these to normal neural development occurring during the adolescent period to establish how meth may target maturing regions and related neurochemistry...
November 8, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29051727/syvn1-an-erad-e3-ubiquitin-ligase-is-involved-in-gabaa%C3%AE-1-degradation-associated-with-methamphetamine-induced-conditioned-place-preference
#7
Dong-Liang Jiao, Yan Chen, Yao Liu, Yun-Yue Ju, Jian-Dong Long, Jiang Du, Chang-Xi Yu, Yu-Jun Wang, Min Zhao, Jing-Gen Liu
Abuse of methamphetamine (METH), a powerful addictive amphetamine-type stimulants (ATS), is becoming a global public health problem. The gamma-aminobutyric acid (GABA)ergic system plays a critical role in METH use disorders. By using rat METH conditioned place preference (CPP) model, we previously demonstrated that METH-associated rewarding memory formation was associated with the reduction of GABAAα1 expression in the dorsal straitum (Dstr), however, the underlying mechanism was unclear. In the present study, we found that METH-induced CPP formation was accompanied by a significant increase in the expression of Synovial apoptosis inhibitor 1 (SYVN1), an endoplasmic reticulum (ER)-associated degradation (ERAD) E3 ubiquitin ligase, in the Dstr...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28960736/safety-risk-and-aggression-health-professionals-experiences-of-caring-for-people-affected-by-methamphetamine-when-presenting-for-emergency-care
#8
Kim Usher, Debra Jackson, Cindy Woods, Jan Sayers, Rachel Kornhaber, Michelle Cleary
The crystalline form of methamphetamine, commonly known as crystal meth (crystal methamphetamine) or ICE, is a highly-addictive and powerful stimulant. Users of crystal meth often require emergency care, and are associated with a substantial burden of care by emergency care providers. The aim of the present qualitative study was to explore health professionals' experiences of providing care for patients affected by ICE who presented to the emergency department (ED). Nine semistructured interviews were conducted...
October 2017: International Journal of Mental Health Nursing
https://www.readbyqxmd.com/read/28939767/dopamine-transporter-phosphorylation-site-threonine-53-is-stimulated-by-amphetamines-and-regulates-dopamine-transport-efflux-and-cocaine-analog-binding
#9
Sathya Challasivakanaka, Juan Zhen, Margaret E Smith, Maarten E A Reith, James D Foster, Roxanne A Vaughan
The dopamine transporter (DAT) controls the spatial and temporal dynamics of dopamine neurotransmission through reuptake of extracellular transmitter and is a target for addictive compounds such as cocaine, amphetamine (AMPH), and methamphetamine (METH). Reuptake is regulated by kinase pathways and drug exposure, allowing for fine-tuning of clearance in response to specific conditions, and here we examine the impact of transporter ligands on DAT residue Thr53, a proline-directed phosphorylation site previously implicated in AMPH-stimulated efflux mechanisms...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28890714/gut-microbiota-analysis-in-rats-with-methamphetamine-induced-conditioned-place-preference
#10
Tingting Ning, Xiaokang Gong, Lingling Xie, Baomiao Ma
Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP) were analyzed through 16S rRNA gene sequencing...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28870635/cannabidiol-inhibits-priming-induced-reinstatement-of-methamphetamine-in-rem-sleep-deprived-rats
#11
Saeideh Karimi-Haghighi, Abbas Haghparast
Methamphetamine (METH) is a widely abused and a severely addictive psychostimulant. Relapse is the main cause of concern when treating addiction. It could manifest after a long period of abstinence. Previous studies showed that there is a strong connection between sleep impairment and relapse. Also, it has been reported that cannabidiol might be a potential treatment for drug craving and relapse. In this study, we used conditioned place preference (CPP) to investigate whether Cannabidiol (CBD), a phytocannabinoid, can prevent METH-induced reinstatement in Rapid Eye Movement Sleep Deprived (RSD) rats...
September 1, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28870523/antagonism-of-mglu2-3-receptors-in-the-nucleus-accumbens-prevents-oxytocin-from-reducing-cued-methamphetamine-seeking-in-male-and-female-rats
#12
Aurelien Bernheim, Kah-Chung Leong, Carole Berini, Carmela M Reichel
Methamphetamine (meth) addiction is a prevalent health concern worldwide, yet remains without approved pharmacological treatments. Preclinical evidence suggests that oxytocin may decrease relapse, but the neuronal underpinnings driving this effect remain unknown. Here we investigate whether oxytocin's effect is dependent on presynaptic glutamatergic regulation in the nucleus accumbens core (NAcore) by blocking metabotropic glutamate receptors 2/3 (mGluR2/3). Male and female Sprague-Dawley rats self-administered meth or sucrose on an escalating fixed ratio, followed by extinction and cue-induced reinstatement sessions...
October 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28859474/aggregated-single-walled-carbon-nanotubes-absorb-and-deform-dopamine-related-proteins-based-on-molecular-dynamics-simulations
#13
Yi Yu, Huiyong Sun, Keith Gilmore, Tingjun Hou, Suidong Wang, Youyong Li
Single-walled carbon nanotubes (SWCNTs) have attracted considerable attention owing to their applications in various fields such as biotechnology and biomedicine. Recently, aggregated SWCNTs have shown more significant effects on the treatment of methamphetamine addiction (Nat. Nanotech. 2016, 11, 613). However, the mechanisms underlying these actions are unclear. By using all-atom molecular dynamics simulations, we investigate the effects of single and aggregated SWCNTs (single-(10,10)CNT, aggregated-7-(10,10)CNTs, and single-(35,35)CNT with the same diameter as that of the aggregated one) on the activity of dopamine-related proteins [tyrosine hydroxylase (TyrOH) and dopamine transporter (DAT), which are related to the synthesis and transport of dopamine, respectively]...
September 27, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28844119/the-role-of-hint1-in-methamphetamine-induced-conditioned-place-preference
#14
Ju-Ping Li, Peng Liu, Gang Lei, Zheng Chu, Fei Liu, Chao-Feng Shi, Yong-Hui Dang, Teng Chen
Drug addiction is a chronically relapsing disorder in humans; yet, the underlying mechanism remained unclear. Recent studies suggested that the histidine triad nucleotide binding protein 1 (HINT1) may play significant roles in diverse neuropsychiatric diseases including drug addiction. In our present study, we used different batches of mice to establish the different stages of methamphetamine (METH)-induced conditioned place preference (CPP) to explore the dynamic changes throughout the process of addiction in different brain regions, including prefrontal cortex (PFC), nucleus accumbens (NAc), corpus striatum (CPu), and hippocampus (Hip)...
August 26, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28842817/methamphetamine-induces-tet1-and-tet3-dependent-dna-hydroxymethylation-of-crh-and-avp-genes-in-the-rat-nucleus-accumbens
#15
Subramaniam Jayanthi, Betina Gonzalez, Michael T McCoy, Bruce Ladenheim, Veronica Bisagno, Jean Lud Cadet
Methamphetamine (METH) addiction is a biopsychosocial disorder that is accompanied by multiple relapses even after prolonged abstinence, suggesting the possibilities of long-lasting maladaptive epigenetic changes in the brain. Here, we show that METH administration produced time-dependent increases in the expression of corticotropin-releasing hormone (Crh/Crf), arginine vasopressin (Avp), and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) mRNAs in the rat nucleus accumbens (NAc). Chromatin immunoprecipitation (ChIP) assays revealed that METH increased the abundance of phosphorylated CREB (pCREB) at the promoter of Cartpt but not at Avp or Crh DNA sequences...
August 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28782589/the-role-of-thioredoxin-1-in-resisting-methamphetamine-induced-rewarding-effect
#16
Mengbing Huang, Lingpin Kong, Lihua Yang, Xiang Li, Xiaoshuang Zhou, Ye Li, Jie Bai
Methamphetamine (METH) is a highly addictive drug of abuse which induces behavioral sensitization and rewarding effects. Thioredoxin-1 (Trx-1) is a redox protein and plays roles in regulating activity of transcription factor, such as cAMP responsive element-binding protein (CREB), AP-1, p53, is emerging as an important modulator of neuronal function. It has been reported that Trx-1 is involved in morphine dependence. In this study, we examined the rewarding effect after METH administration by conditioned place preference (CPP) of mice, and detected the levels of dopamine and the activity of cAMP responsive element-binding protein (CREB), the expressions of ΔFosB and cyclin-dependent kinase 5 (CDK5) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mice...
January 30, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28731367/methamphetamine-causes-photoreceptor-cell-damage-through-promoting-polarization-of-macrophages-and-inducing-inflammatory-response
#17
Aihui Zhang, Laiwei Wu, Zilin Chen, Guoqiang Huang, Xiaohe Lu
Classically activated macrophages (M1) are proinflammatory effectors and closely related to the progression of neurotoxicity. As a powerful psychostimulant and addictive drug, methamphetamine (Meth) abuse could result in long-lasting abnormalities in retina. This study investigated the effect of Meth at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by Meth on 661 W cells after coculturing with RAW264.7 macrophage...
September 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28686721/systemic-pd149163-a-neurotensin-receptor-1-agonist-decreases-methamphetamine-self-administration-in-dba-2j-mice-without-causing-excessive-sedation
#18
Amanda L Sharpe, Erika Varela, Michael J Beckstead
Methamphetamine (METH) is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area. Previous studies in rats suggest that neurotensin agonism decreases METH self-administration, but these studies did not examine the effect of neurotensin agonism on the pattern of self-administration or open field locomotion...
2017: PloS One
https://www.readbyqxmd.com/read/28681200/microrna-expression-signature-of-methamphetamine-use-and-addiction-in-the-rat-nucleus-accumbens
#19
Maw Shin Sim, Tomoko Soga, Vijayapandi Pandy, Yuan Seng Wu, Ishwar S Parhar, Zahurin Mohamed
Methamphetamine (METH) is a highly addictive psycho-stimulant that induces behavioral changes due to high level of METH-induced dopamine in the brain. Nucleus accumbens (NAc) plays an important role in these changes, especially in drug addiction. However, little is known about the underlying molecular mechanisms of METH-induced addiction. The objective of this study was to establish a behavioral model of METH use and addiction using escalating doses of METH over 15 days and to determine the global miRNA expression profiling in NAc of METH-addicted rats...
December 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28645061/the-neurochemical-consequences-of-methamphetamine-self-administration-in-male-and-female-rats
#20
Andrew Johansen, Lisa M McFadden
BACKGROUND: Methamphetamine (METH) is an addictive substance that is used in both males and females. Few preclinical studies have focused on understanding sex-differences in the neurochemical consequences of contingent METH. The purpose of the current study was to investigate potential sex-differences in the neurochemical consequences of METH self-administration. METHODS: Male and female adult rats were given extended access to METH or saline self-administration for 7d...
September 1, 2017: Drug and Alcohol Dependence
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