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https://www.readbyqxmd.com/read/28433511/design-synthesis-and-pharmacological-evaluation-of-4-azolyl-benzamide-derivatives-as-novel-gpr52-agonists
#1
Kazuyuki Tokumaru, Yoshiteru Ito, Izumi Nomura, Takashi Nakahata, Yuji Shimizu, Emi Kurimoto, Kazunobu Aoyama, Kazuyoshi Aso
G protein-coupled receptor 52 (GPR52) agonists are expected to improve the symptoms of psychiatric disorders. During exploration for a novel class of GPR52 agonists with good pharmacokinetic profiles, we synthesized 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (4u; half maximal effective concentration (EC50)=75nM, maximal response (Emax)=122%) starting from a high-throughput screening hit 3 (EC50=470nM, Emax=56%). The structural features of a reported GPR52 agonist were applied to 3, led to design 4-azolylbenzamides as novel GPR52 agonists...
April 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28421529/suppression-of-methamphetamine-self-administration-by-ketamine-pre-treatment-is-absent-in-the-methylazoxymethanol-mam-rat-model-of-schizophrenia
#2
Jana Ruda-Kucerova, Zuzana Babinska, Tibor Stark, Vincenzo Micale
Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration...
April 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28387990/cdh13-and-adipoq-gene-knockout-alters-instrumental-and-pavlovian-drug-conditioning
#3
Christopher P King, Leah Militello, Amy Hart, Celine L St Pierre, Emily Leung, Cassandra L Versaggi, Nathaniel Roberson, James Catlin, Abraham A Palmer, Jerry B Richards, Paul J Meyer
Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knock-out rats and AdipoQ knock-out mice using intravenous cocaine self-administration and conditioned place preference paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/-) and knock-out (-/-) rats showed increased cue-induced reinstatement compared to wild-type rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype...
April 7, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28386698/comparison-of-some-behavioral-effects-of-d-and-l-methamphetamine-in-adult-male-rats
#4
Justin N Siemian, Zhaoxia Xue, Bruce E Blough, Jun-Xu Li
RATIONALE: Both l- and d-methamphetamine (l- and d-MA) are more potent to release norpepinephrine (NE) than dopamine, and the selectivity is greater for l-MA than d-MA. Little is known of the in vivo pharmacology of l-MA. OBJECTIVE: This study compared the effects of l-MA and d-MA in assays of nociception, behavioral disruption, and impulsivity. METHODS: Antinociceptive effects of d- and l-MA were examined in two pain assays: the warm water tail withdrawal test for acute nociception and the von Frey test in complete Freund's adjuvant (CFA)-treated rats for chronic inflammatory pain...
April 6, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28359886/sex-differences-in-the-strategies-of-spatial-learning-in-prenatally-exposed-rats-treated-with-various-drugs-in-adulthood
#5
Eva Macúchová, Kateryna Nohejlová, Mária Ševčíková, Ivana Hrebíčková, Romana Šlamberová
In the present study we investigated the sex differences in the effect of adult long-term drug treatment on cognitive functions of Wistar rats, which were prenatally exposed to MA (5mg/kg) or saline. Cognitive functions were tested as an ability of spatial learning in the Morris Water Maze (MWM), which consisted of three types of tests: "Place Navigation Test"; "Probe Test", and "Memory Recall Test". Adult animals were injected daily, after completion of the last trial, either with saline or cocaine (COC; 5mg/kg), MDMA (3,4-methylenedioxy-methamphetamine; 5mg/kg), morphine (MOR; 5mg/kg), or delta-9-tetrahydrocannabinol (THC; 2mg/kg)...
March 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28351548/behavioral-sensitization-to-methamphetamine-induces-specific-interneuronal-mrna-pathology-across-the-prelimbic-and-orbitofrontal-cortices
#6
Travis A Wearne, Lindsay M Parker, Jane L Franklin, Ann K Goodchild, Jennifer L Cornish
Schizophrenia is associated with significant pathophysiological changes to interneurons within the prefrontal cortex (PFC), with mRNA and protein changes associated with the GABA network localized to specific interneuron subtypes. Methamphetamine is a commonly abused psychostimulant that can induce chronic psychosis and symptoms that are similar to schizophrenia, suggesting that chronic METH induced psychosis may be associated with similar brain pathology to schizophrenia in the PFC. The aim of this study, therefore, was to examine mRNA expression of interneuron markers across two regions of the PFC (prelimbic (PRL) and orbitofrontal cortices (OFC)) following METH sensitization, an animal model of METH psychosis...
March 27, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28348387/a-synthetic-small-molecule-isoxazole-9-protects-against-methamphetamine-relapse
#7
M H Galinato, J W Lockner, M J Fannon-Pavlich, J C Sobieraj, M C Staples, S S Somkuwar, A Ghofranian, S Chaing, A I Navarro, A Joea, B W Luikart, K D Janda, C Heyser, G F Koob, C D Mandyam
Adult neurogenesis in the dentate gyrus (DG) is strongly influenced by drug-taking behavior and may have a role in the etiology of drug-seeking behavior. However, mechanistic studies on the relationship of neurogenesis on drug seeking are limited. Outbred Wistar rats experienced extended access methamphetamine self-administration and individual differences in drug taking defined animals with higher preferred and lower preferred levels of drug intake. Forced abstinence from higher preferred levels of drug taking enhanced neurogenesis and neuronal activation of granule cell neurons (GCNs) in the DG and produced compulsive-like drug reinstatement...
March 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28341135/methamphetamine-induces-hepatotoxicity-via-inhibiting-cell-division-arresting-cell-cycle-and-activating-apoptosis-in%C3%A2-vivo-and-in%C3%A2-vitro-studies
#8
Qi Wang, Li-Wen Wei, Huan-Qin Xiao, Ye Xue, Si-Hao Du, Yun-Gang Liu, Xiao-Li Xie
Methamphetamine (METH) resulted in acute hepatic injury. However, the underlying mechanisms have not been fully clarified. In the present study, rats were treated with METH (15 mg/kg B.W.) for 8 injections (i.p.), and the levels of alanine transaminase, asparatate transaminase and ammonia in serum were significantly elevated over those in the control group, suggesting hepatic injury, which was evidenced by histopathological observation. Analysis of the liver tissues with microarray revealed differential expressions of a total of 332 genes in METH-treated rats...
March 21, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28339044/suppression-of-nuclear-factor-erythroid%C3%A2-2%C3%A2-related-factor-2%C3%A2-mediated-antioxidative-defense-in-the-lung-injury-induced-by-chronic-exposure-to-methamphetamine-in-rats
#9
Yang Bai, Yun Wang, Ming Liu, Yu-Han Gu, Bin Jiang, Xu Wu, Huai-Liang Wang
The imbalance between oxidative stress and antioxidant defense is important in the pathogenesis of lung diseases. Nuclear factor erythroid‑2‑related factor 2 (Nrf2) is a key transcriptional factor that regulates the antioxidant response. The purpose of the present study was to investigate whether Nrf2‑mediated antioxidative defense is involved in methamphetamine (MA)‑induced lung injury in rats. Following establishment of chronic MA toxicity in rats, Doppler ultrasonic detection was used to measure the changes of physiological indexes, followed by hematoxylin and eosin staining, ELISA and western blot analysis...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28330826/the-influence-of-methamphetamine-on-maternal-behavior-and-development-of-the-pups-during-the-neonatal-period
#10
Mária Ševčíková, Ivana Hrebíčková, Eva Macúchová, Romana Šlamberová
Since it enters breast milk, methamphetamine (MA) abuse during lactation can not only affect the quality of maternal behavior but also postnatal development of pups. The aim of the present study was to examine the effect of injected MA (5mg/kg) on maternal behavior of rats and the differences in postnatal development, during postnatal days (PD) 1-11, of pups when the pups were directly exposed (i.e., injected) to MA or received MA indirectly via breast milk. Maternal behavior was examined using observation test (PD 1-22) and pup retrieval test (PD 1-12)...
March 19, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28322983/the-relationship-between-fear-extinction-and-resilience-to-drug-dependence-in-rats
#11
Masaharu Ueno, Kazuo Yamada, Yukio Ichitani
Some individuals recover quickly from stressful events, while others do not; this suggests that there are individual differences in stress resilience. Previous studies in rats have shown that an animal's ability to extinguish conditioned fear can predict their stress resilience. In the present study, we investigated whether rats who are resilient or vulnerable to fear conditioning would consistently show resilient or vulnerable behaviors in other behavioral tests. Male Wistar-Imamichi rats were subjected to a series of behavioral tests, including open field, conditioned place-preference (CPP), forced swim and auditory fear conditioning...
March 18, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28303170/tbhq-alleviated-endoplasmic-reticulum-stress-apoptosis-and-oxidative-stress-by-perk-nrf2-crosstalk-in-methamphetamine-induced-chronic-pulmonary-toxicity
#12
Yun Wang, Yu-Han Gu, Ming Liu, Yang Bai, Li-Ye Liang, Huai-Liang Wang
Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28301174/differential-characteristics-of-ketamine-self-administration-in-the-olfactory-bulbectomy-model-of-depression-in-male-rats
#13
Zuzana Babinska, Jana Ruda-Kucerova
Ketamine has been extensively studied for its antidepressant potential, with promising results in both preclinical and clinical studies. However, concerns regarding its abuse liabilities greatly limit its potential to become an approved treatment for depression. Therefore, a better understanding the risks and benefits of ketamine use in depression is needed. This study aimed to assess the characteristics of operant intravenous (IV) ketamine self-administration and relapse-like behavior in the olfactory bulbectomy (OBX) model of depression in male rats...
April 2017: Experimental and Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28293389/exploring-the-effect-of-intravenous-lipid-emulsion-in-acute-methamphetamine-toxicity
#14
Ameneh Ghadiri, Leila Etemad, Mohammad Moshiri, Seyed Adel Moallem, Amir Hossein Jafarian, Farzin Hadizadeh, Mahmoud Seifi
OBJECTIVES: The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning. MATERIALS AND METHODS: Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28287691/effects-of-housing-on-methamphetamine-induced-neurotoxicity-and-spatial-learning-and-memory
#15
Arnold Gutierrez, Sarah A Jablonski, Robyn M Amos-Kroohs, Anna C Barnes, Michael T Williams, Charles V Vorhees
Severe stress potentiates methamphetamine (MA) neurotoxicity. However, whether moderate stress increases or decreases the neurotoxic effects of MA is unknown. We assessed the effects of MA (4 × 10 mg/kg at 2 h intervals) in combination with prior barren-cage housing in adult male Sprague-Dawley rats on monoamines and glial fibrillary acid protein (GFAP) in one cohort and spatial learning and memory in the Morris water maze in another cohort. MA reduced dopamine (DA) and serotonin (5-HT) in the neostriatum and nucleus accumbens, 5-HT in the hippocampus, and increased GFAP in neostriatum and nucleus accumbens compared with saline controls...
March 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28284948/compulsive-methamphetamine-taking-under-punishment-is-associated-with-greater-cue-induced-drug-seeking-in-rats
#16
Oscar V Torres, Subramanian Jayanthi, Bruce Ladenheim, Michael T McCoy, Irina N Krasnova, Jean Lud Cadet
Methamphetamine (METH) addicts lose control over drug consumption despite suffering multiple adverse medicolegal consequences. To mimic the negative events associated with drug addiction in humans, we recently introduced a rat model of self-administration (SA) with response-contingent punishment on METH intake. These procedures allowed us to distinguish between two addiction-like phenotypes in rats, those that sustained METH taking despite negative consequences (shock-resistant, SR) and rats that significantly reduced their METH intake (shock-sensitive, SS)...
March 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28274858/neurotoxicity-induced-by-methamphetamine-heroin-combination-in-pc12-cells
#17
Xiang Tian, Qin Ru, Qi Xiong, Kai Yue, Lin Chen, Baomiao Ma, Weimin Gan, Yuanren Si, Huqiao Xiao, Chaoying Li
Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. The combination of psychostimulants and opioids produces more serious effects than either drug alone and is responsible for numerous deaths. In recent years, owing to its increased use, methamphetamine (METH), a psychostimulant, has become a popular choice for use in combination with opioids, especially heroin. However, little is known about the neurotoxicity of METH/heroin combination. The aims of this study were to evaluate whether METH/heroin combination was more neurotoxic than either drug alone and analyze the possible neurotoxic mechanisms using rat pheochromocytoma (PC12) cells...
March 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28272323/neurotoxic%C3%A2-doses%C3%A2-of%C3%A2-chronic%C3%A2-methamphetamine%C3%A2-trigger%C3%A2-retrotransposition%C3%A2-of%C3%A2-the%C3%A2-identifier%C3%A2-element%C3%A2-in%C3%A2-rat%C3%A2-dorsal%C3%A2-dentate%C3%A2-gyrus
#18
Anna Moszczynska, Kyle J Burghardt, Dongyue Yu
Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was to determine whether neurotoxic doses of binge or chronic methamphetamine (METH) trigger retrotransposition of the identifier (ID) element, a member of the rat SINE family, in the dentate gyrus genomic DNA...
March 6, 2017: Genes
https://www.readbyqxmd.com/read/28249787/effects-of-prolonged-abstinence-from-meth-on-the-hippocampal-bdnf-levels-neuronal-numbers-and-apoptosis-in-methamphetamine-sensitized-rats
#19
Samira Hajheidari, Hamid Reza Sameni, Ahmad Reza Bandegi, Hossein Miladi-Gorji
Methamphetamine (METH) use is associated with neuronal damage in various regions of brain, while effects of prolonged abstinence on METH-induced damage are not quite clear. This study evaluated serum and hippocampal BDNF levels, neuronal numbers and apoptosis in METH-sensitized and abstinent rats. Rats were sensitized to METH (2mg/kg, daily/18 days, s.c.). All rats were evaluated for neuron counting, the TUNEL test and serum and hippocampal BDNF levels after 30 days of forced abstinence from METH. The results showed that increased BDNF levels in the hippocampus and serum of METH-sensitized rats returned to control level after 30 days of abstinence...
February 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28243847/effect-of-methamphetamine-exposure-during-pregnancy-and-lactation-on-polysialic-acid-neural-cell-adhesion-molecule-expression-in-rat-s-offspring-hippocampus
#20
Fariba Baei, Aliakbar Rajabzadeh, Javad Bagheri, Zahra Jalayeri, Alireza Ebrahimzadeh-Bideskan
Pregnant women constitute about half the users of methamphetamine (MA), in whom the consumption may continue during breastfeeding. This study aimed to evaluate the effects of MA use during pregnancy and lactation on the hippocampus of pups. 35 pregnant Wistar rats were divided into seven groups, including three experimental groups daily administered with 5 mg/kg of MA (i.p.) during the prenatal and/or postnatal period (PND1-22). In addition, three sham control groups received normal saline at the same dose, and one normal control group received no interventions since early pregnancy until the end of lactation...
February 27, 2017: Metabolic Brain Disease
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