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methamphetamine rat

Hancheng Li, Chan Li, Yuting Zhou, Chaohua Luo, Jingying Ou, Jing Li, Zhixian Mo
Drug abuse is a public health and social problem. A number of studies have reported that drug addiction is associated with microRNAs (miRNAs). By comparing the expression of miRNAs in the serum exosomes of methamphetamine-dependent and ketamine-dependent rats, the aim of the present study was to provide insights into the miRNA-mediated associations between the two groups. Published results on conditioned place preference (CPP) in rats conditioned by methamphetamine and ketamine were replicated. The expression of miRNAs in serum exosomes were determined by gene-chip sequencing...
April 2018: Experimental and Therapeutic Medicine
Rubén García-Cabrerizo, Cristian Bis-Humbert, M Julia García-Fuster
A recent study from our laboratory demonstrated that binge methamphetamine induced hippocampal cell damage (i.e., impaired cell genesis) in rats when administered specifically during late adolescence (postnatal day, PND 54-57) and evaluated 24 h later (PND 58). The results also suggested a possible role for brain-derived neurotrophic factor (BDNF) regulating cell genesis and survival. This subsequent study evaluated whether these effects persisted in time as measured following prolonged withdrawal. Male Sprague-Dawley rats were treated (i...
February 28, 2018: Neurotoxicology
Enquan Xu, Jianuo Liu, Han Liu, Xiaobei Wang, Huangui Xiong
Methamphetamine (Meth) is an addictive psychostimulant abused worldwide. Ample evidence indicate that chronic abuse of Meth induces neurotoxicity via microglia-associated neuroinflammation and the activated microglia present in both Meth-administered animals and human abusers. The development of anti-neuroinflammation as a therapeutic strategy against Meth dependence promotes research to identify inflammatory pathways that are specifically tied to Meth-induced neurotoxicity. Currently, the exact mechanisms for Meth-induced microglia activation are largely unknown...
February 28, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Robert N Hughes, Jennifer J Hamilton
For fourteen days, male and female PVG/c hooded rats were provided continuously with either pure drinking water, or water containing caffeine in a quantity approximating a daily dose of 31.1 mg/kg. Then at intervals of 3 days, they were administered 1, 2 mg/kg methamphetamine (MA) or saline before being tested for anxiety-related behavior in a zero maze or a light/dark box, or their short-term spatial memory was assessed in a Y maze following introduction of a novel brightness change in one of the arms. Each rat experienced each type of apparatus with the same acute MA or saline treatment while still exposed to chronic caffeine or pure drinking water...
February 21, 2018: Behavioural Brain Research
Shasha Xu, Shaoang Tu, Jinlong Gao, Jia Liu, Zhirui Guo, Jinming Zhang, Xingdang Liu, Jianhui Liang, Yiyun Huang, Mei Han
BACKGROUND: Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function...
February 23, 2018: BMC Complementary and Alternative Medicine
Ashlea F Dassanayake, Juan J Canales
There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial...
February 13, 2018: Neuroscience Letters
Masato Nakashima, Haruka Imada, Eri Shiraishi, Yuki Ito, Noriko Suzuki, Maki Miyamoto, Takahiko Taniguchi, Hiroki Iwashita
The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N-methyl-D-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain penetrant PDE2A inhibitor, (N-{(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide) (TAK-915) as a novel treatment for schizophrenia...
February 13, 2018: Journal of Pharmacology and Experimental Therapeutics
Arnold Gutierrez, Michael T Williams, Charles V Vorhees
Methamphetamine (MA) alters dopamine markers and cognitive function in heavy users. In rodents, there are MA dosing regimens that induce concordant effects using repeated administration at spaced intervals. These regimens are effective but complicate experiments designed to disentangle the effects of the drug on different brain regions in relation to their cognitive effects because of treatment spacing. In an effort to simplify the model, we tested whether a single dose of MA could induce the same monoamine and cognitive effects as multiple, spaced dosing without affecting survival...
February 9, 2018: Neurotoxicity Research
Na-Ra Lee, Guangrong Zheng, Peter A Crooks, Michael T Bardo, Linda P Dwoskin
Despite increased methamphetamine use worldwide, pharmacotherapies are not available to treat methamphetamine use disorder. The vesicular monoamine transporter-2 (VMAT2) is an important pharmacological target for discovery of treatments for methamphetamine use disorder. VMAT2 inhibition by the natural product, lobeline, reduced methamphetamine-evoked dopamine release, methamphetamine-induced hyperlocomotion, and methamphetamine self-administration in rats. Compared to lobeline, lobelane exhibited improved affinity and selectivity for VMAT2 over nicotinic acetylcholine receptors...
February 9, 2018: AAPS Journal
Kazunori Suzuki, Akina Harada, Hirobumi Suzuki, Clizia Capuani, Annarosa Ugolini, Mauro Corsi, Haruhide Kimura
Activation of indirect pathway medium spiny neurons (MSNs) via promotion of cAMP production is the principal mechanism of action of current antipsychotics with dopamine D2 receptor antagonism. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a novel phosphodiesterase 10A inhibitor that activates both direct and indirect pathway MSNs through increasing both cAMP and cGMP levels by inhibition of their degradation. The activation of indirect pathway MSNs through the distinct mechanism of action of these drugs raises the possibility of augmented pharmacological effects by combination therapy...
February 2018: Pharmacology Research & Perspectives
Xuan Li, Maria B Carreria, Kailyn R Witonsky, Tamara Zeric, Olivia M Lofaro, Jennifer M Bossert, Jianjun Zhang, Felicia Surjono, Christopher T Richie, Brandon K Harvey, Hyeon Son, Christopher W Cowan, Eric J Nestler, Yavin Shaham
BACKGROUND: Methamphetamine (meth) seeking progressively increases after withdrawal (incubation of meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in the rat dorsal striatum and incubation of meth craving. Here we used viral constructs to study the causal role of dorsal striatum HDAC5 in this incubation. METHODS: In experiment 1 (overexpression), we injected an adeno-associated virus bilaterally into dorsal striatum to express either green fluorescent protein (control) or a mutant form of HDAC5, which strongly localized to the nucleus...
December 29, 2017: Biological Psychiatry
Erin M Miller, Jorge E Quintero, Francois Pomerleau, Peter Huettl, Greg A Gerhardt, Paul E A Glaser
Glutamate dysfunction has been implicated in a number of substance of abuse studies, including cocaine and methamphetamine. Moreover, in attention-deficit/hyperactivity disorder (ADHD), it has been discovered that when the initiation of stimulant treatment occurs during adolescence, there is an increased risk of developing a substance use disorder later in life. The spontaneously hypertensive rat (SHR) serves as a phenotype for ADHD and studies have found increased cocaine self-administration in adult SHRs when treated with the stimulant methylphenidate (MPH) during adolescence...
February 3, 2018: Neurochemical Research
Sean B Dolan, Zhenglan Chen, Renqi Huang, Michael B Gatch
This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution...
January 26, 2018: Neuropharmacology
Xuan Li, Kailyn Witonsky, Olivia M Lofaro, Felicia Surjono, Jianjun Zhang, Jennifer M Bossert, Yavin Shaham
Relapse to methamphetamine (Meth) seeking progressively increases after withdrawal from drug self-administration (incubation of Meth craving). We previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1 receptors (D1Rs) in this incubation. Here, we studied the role of afferent glutamatergic projections into DMS and local D1R-glutamate interaction in this incubation in male rats.We first measured projection-specific activation on day 30 relapse test by using CTb (retrograde tracer) + Fos (activity marker) double-labeling in projection areas...
January 25, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jickssa M Gemechu, Akhil Sharma, Dongyue Yu, Yuran Xie, Olivia M Merkel, Anna Moszczynska
Mutations in parkin gene (Park2) are linked to early-onset autosomal recessive Parkinson's disease (PD) and young-onset sporadic PD. Park2 knockout (PKO) rodents; however, do not display neurodegeneration of the nigrostriatal pathway, suggesting age-dependent compensatory changes. Our goal was to examine dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to characterize compensatory mechanisms that may have occurred within the system. The striata form wild type (WT) and PKO Long Evans male rats were assessed for the levels of DAergic markers, for monoamine oxidase (MAO) A and B activities and levels, and for the levels of their respective preferred substrates, serotonin (5-HT) and ß-phenylethylamine (ß-PEA)...
January 24, 2018: Scientific Reports
Melissa H Galinato, Yoshio Takashima, McKenzie J Fannon, Leon W Quach, Roberto J Morales Silva, Karthik K Mysore, Michael J Terranova, Rahul R Dutta, Ryan W Ostrom, Sucharita S Somkuwar, Chitra D Mandyam
Abstinence from methamphetamine addiction enhances proliferation and differentiation of neural progenitors and increases adult neurogenesis in the dentate gyrus (DG). We hypothesized that neurogenesis during abstinence contributes to context-driven drug-seeking behaviors. To test this hypothesis, the pharmacogenetic rat model (GFAP-TK rats) was used to conditionally and specifically ablate neurogenesis in the DG. Male GFAP-TK rats were trained to self-administer methamphetamine or sucrose and were administered the antiviral drug valganciclovir (Valcyte) to produce apoptosis of actively dividing GFAP-type 1 stem-like cells to inhibit neurogenesis during abstinence...
January 23, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nam Jun Kim, Yeonhee Ryu, Bong Hyo Lee, Suchan Chang, Yu Fan, Young S Gwak, Chae Ha Yang, Kyle B Bills, Scott C Steffensen, Jin Suk Koo, Eun Young Jang, Hee Young Kim
Methamphetamine (METH) increases metabolic neuronal activity in the mesolimbic dopamine (DA) system and mediates the reinforcing effect. To explore the underlying mechanism of acupuncture intervention in reducing METH-induced behaviors, we investigated the effect of acupuncture on locomotor activity, ultrasonic vocalizations, extracellular DA release in the nucleus accumbens (NAcs) using fast-scan cyclic voltammetry and alterations of brain temperature (an indicator of local brain metabolic activity) produced by METH administration...
January 23, 2018: Addiction Biology
A Holubová, M Ševčíková, E Macúchová, I Hrebíčková, M Pometlová, R Šlamberová
Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s...
December 30, 2017: Physiological Research
R Šlamberová, J Rudá-Kučerová, Z Babinská, M Ševčíková
Olfactory bulbectomy in rodents is considered a putative model of depression. Depression is often associated with drug addiction. Our previous studies demonstrated that methamphetamine (MA) administration to rat mothers affects both, mothers and their pups. The aim of the present study was to examine the effect of bulbectomy, as a model of depression, and MA administration on behavior of rat mothers and postnatal development of their pups. Adult female Wistar rats were randomly divided into two groups: bulbectomized (OBX) and sham-operated (SH)...
December 30, 2017: Physiological Research
Pouran Malekzadeh, Jackie Hu, Alexander J Sandweiss, Nina Ameli, Philippe Bierny, Tally M Largent-Milnes, Todd W Vanderah, Farshad Shirazi
Context: Methamphetamine (MA) toxicity is a major health concern causing agitation, hyperkinesia, hyperthermia, and even death, affecting 24.7 million people worldwide. It has been observed that MA generates movement disorders in children similar to that of scorpion envenomation. Four cases have been reported where MA intoxication in children were both subjectively and objectively improved as indicated by the reversal of nystagmus and movement disorders following administration of Centruroides antivenom (AV) therapy...
April 2017: Journal of Pharmaceutics & Pharmacology
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