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Amphetamines signaling pathway

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https://www.readbyqxmd.com/read/29580892/cocaine-and-amphetamine-regulated-transcript-peptide-cart-induced-reward-behavior-is-mediated-via-g-i-o-dependent-phosphorylation-of-pka-erk-creb-pathway
#1
Amita R Somalwar, Amit G Choudhary, Pravesh R Sharma, Nagalakshmi B, Sneha Sagarkar, Amul J Sakharkar, Nishikant K Subhedar, Dadasaheb M Kokare
Although the role of cocaine- and amphetamine-regulated transcript peptide (CART) in modulating the mesolimbic reward pathway has been suggested, underlying cellular mechanisms have not been elucidated. Herein, we investigate the involvement of Gi/o dependent protein kinase A (PKA)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) signaling in CART induced reward behavior. The rat was implanted with a stimulating electrode targeted at the lateral hypothalamus (LH)-medial forebrain bundle (MFB) and conditioned to intracranial self-stimulation (ICSS) in an operant chamber...
March 23, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29511968/amphetamine-neurotoxicity-in-pc12-cells-through-the-pp2a-akt-gsk3%C3%AE-pathway
#2
Wenji He, Xinyu Yan, Sanqiang Pan
Amphetamine (AMPH) abuse can influence neuropsychiatric disorders and cell apoptosis by interfering with the protein kinase B/ glycogen synthase kinase 3 beta (AKT/GSK3β) pathway. However, the mechanisms underlying this regulation are poorly understood. Using PC12 cells, we found that AMPH inhibited AKT and GSK-3β phosphorylation levels and increased total GSK-3β levels. Furthermore, AMPH caused an increase in the activity of protein phosphatase 2 (PP2A), a signaling protein upstream of AKT, which in turn inhibited phosphorylated AKT levels...
March 6, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29485852/functionally-biased-d2r-antagonists-targeting-the-%C3%AE-arrestin-pathway-to-improve-antipsychotic-treatment
#3
Michel Weïwer, Qihong Xu, Jennifer P Gale, Michael Lewis, Arthur J Campbell, Frederick A Schroeder, Genevieve C Van de Bittner, Michelle Walk, Aldo Amaya, Ping Su, Luka D Ordevic, Joshua R Sacher, Adam Skepner, David Fei, Kelly Dennehy, Shannon Nguyen, Patrick W Faloon, Jose Perez, Jeffrey R Cottrell, Fang Liu, Michelle Palmer, Jen Q Pan, Jacob M Hooker, Yan-Ling Zhang, Edward Scolnick, Florence F Wagner, Edward B Holson
Schizophrenia is a severe neuropsychiatric disease that lacks completely effective and safe therapies. As a polygenic disorder, genetic studies have only started to shed light on its complex etiology. To date, the positive symptoms of schizophrenia are well-managed by antipsychotic drugs, which primarily target the dopamine D2 receptor (D2R). However, these antipsychotics are often accompanied by severe side effects, including motoric symptoms. At D2R, antipsychotic drugs antagonize both G-protein dependent (Gαi/o ) signaling and G-protein independent (β-arrestin) signaling...
March 14, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29454967/sarm1-deletion-restrains-nafld-induced-by-high-fat-diet-hfd-through-reducing-inflammation-oxidative-stress-and-lipid-accumulation
#4
Zhen-Guo Pan, Xu-Sheng An
SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice...
February 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#5
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation, and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29068002/engineered-d2r-variants-reveal-the-balanced-and-biased-contributions-of-g-protein-and-%C3%AE-arrestin-to-dopamine-dependent-functions
#6
Samuel J Rose, Thomas F Pack, Sean M Peterson, Kaitlin Payne, Emiliana Borrelli, Marc G Caron
The dopamine D2 receptor (D2R), like many G-protein-coupled receptors, signals through G-protein- and β-arrestin-dependent pathways. Preferential activation of one of these pathways is termed functional selectivity or biased signaling and is a promising therapeutic strategy. Though biased signaling through D2Rs has been demonstrated, acquiring the mechanistic details of biased D2R/G-protein and D2R/β-arrestin signaling in vivo has been challenging because of the lack of techniques that specifically target these interactions in discrete cell populations...
April 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29063964/phytocannabinoids-modulate-emotional-memory-processing-through-interactions-with-the-ventral-hippocampus-and-mesolimbic-dopamine-system-implications-for-neuropsychiatric-pathology
#7
REVIEW
Roger Hudson, Walter Rushlow, Steven R Laviolette
Growing clinical and preclinical evidence suggests a potential role for the phytocannabinoid cannabidiol (CBD) as a pharmacotherapy for various neuropsychiatric disorders. In contrast, delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, is associated with acute and neurodevelopmental propsychotic side effects through its interaction with central cannabinoid type 1 receptors (CB1Rs). CB1R stimulation in the ventral hippocampus (VHipp) potentiates affective memory formation through inputs to the mesolimbic dopamine (DA) system, thereby altering emotional salience attribution...
October 24, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28690493/emerging-signaling-pathway-in-arcuate-feeding-related-neurons-role-of-the-acbd7
#8
REVIEW
Damien Lanfray, Denis Richard
The understanding of the mechanisms whereby energy balance is regulated is essential to the unraveling of the pathophysiology of obesity. In the last three decades, focus was put on the metabolic role played by the hypothalamic neurons expressing proopiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART) and the neurons co-localizing agouti-related peptide (AgRP), neuropeptide Y (NPY), and gamma-aminobutyric acid (GABA). These neurons are part of the leptin-melanocortin pathway, whose role is key in energy balance regulation...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28545666/mahuannin-b-an-adenylate-cyclase-inhibitor-attenuates-hyperhidrosis-via-suppressing-%C3%AE-2-adrenoceptor-camp-signaling-pathway
#9
Zengyong Wang, Yu Cui, Guoyu Ding, Mengge Zhou, Xiaoyao Ma, Yuanyuan Hou, Min Jiang, Dailin Liu, Gang Bai
BACKGROUND: Based on the traditional application of traditional Chinese Medicines (TCMs), Ephedra Herba (EH) is used to cure cold fever by inducing sweating, whereas Ephedra Radix (ER) is used to treat hyperhidrosis. Although they come from the same plant, Ephedra sinica Stapf, but have play opposing roles in clinical applications. EH is known to contain ephedrine alkaloids, which is the driver of the physiological changes in sweating, heart rate and blood pressure. However, the active pharmacological ingredients (APIs) of ER and the mechanisms by which it restricts sweating remain unknown...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28421658/transcriptional-signatures-of-connectomic-subregions-of-the-human-striatum
#10
L Parkes, B D Fulcher, M Yücel, A Fornito
Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint - a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide brain areas using their connectivity patterns. However, it remains unclear whether these connectomically-defined subregions can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures...
September 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28321131/does-activation-of-midbrain-dopamine-neurons-promote-or-reduce-feeding
#11
L Boekhoudt, T J M Roelofs, J W de Jong, A E de Leeuw, M C M Luijendijk, I G Wolterink-Donselaar, G van der Plasse, R A H Adan
BACKGROUND: Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced DA activity. On the other hand, psychostimulant drugs that increase DA signalling suppress food intake. This poses the questions of how endogenous DA neuronal activity regulates feeding, and whether enhancing DA neuronal activity would either promote or reduce food intake...
July 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28303260/evidence-for-an-additive-neurorestorative-effect-of-simultaneously-administered-cdnf-and-gdnf-in-hemiparkinsonian-rats-implications-for-different-mechanism-of-action
#12
Merja H Voutilainen, Francesca De Lorenzo, Polina Stepanova, Susanne Bäck, Li-Ying Yu, Päivi Lindholm, Eeva Pörsti, Mart Saarma, Pekka T Männistö, Raimo K Tuominen
Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic (DAergic) neurons of the substantia nigra (SN) and the accumulation of intracellular inclusions containing α-synuclein. Current therapies do not stop the progression of the disease, and the efficacy of these treatments wanes over time. Neurotrophic factors (NTFs) are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. CDNF (cerebral dopamine NTF) and GDNF (glial cell line-derived NTF) are able to protect DAergic neurons against toxin-induced degeneration in experimental models of PD...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28284949/inhibition-of-wnt-signalling-dose-dependently-impairs-the-acquisition-and-expression-of-amphetamine-induced-conditioned-place-preference
#13
Farhana Islam, Kathleen Xu, Richard J Beninger
The mechanisms by which dopaminergic neurotransmission in the nucleus accumbens (NAc) is involved in incentive learning produced by rewarding stimuli remain unclear. Recently, Wnt signalling has been implicated in synaptic plasticity and learning and memory. Functional interactions between Wnt and dopamine (DA) signalling has been demonstrated using in vitro and tissue physiology approaches, however there remains a lack of in vivo research into the involvement of Wnt in DA-mediated learning in behaving animals...
March 9, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28264500/geneanalytics-pathway-analysis-and-genetic-overlap-among-autism-spectrum-disorder-bipolar-disorder-and-schizophrenia
#14
Naveen S Khanzada, Merlin G Butler, Ann M Manzardo
Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e...
February 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27720500/stimuli-associated-with-the-presence-or-absence-of-amphetamine-regulate-cytoskeletal-signaling-and-behavior
#15
Bryan F Singer, Nancy Bubula, Magdalena M Przybycien-Szymanska, Dongdong Li, Paul Vezina
Drug-paired stimuli rapidly enlarge dendritic spines in the nucleus accumbens (NAcc). While increases in spine size and shape are supported by rearrangement of the actin cytoskeleton and facilitate the synaptic expression of AMPA-type glutamate receptors, it remains unclear whether drug-related stimuli can influence signaling pathways known to regulate these changes in spine morphology. These pathways were studied in rats trained on a discrimination learning paradigm using subcellular fractionation and protein immunoblotting to isolate proteins within dendritic spine compartments in the NAcc shell...
November 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27524619/genetic-disruption-of-arc-arg3-1-in-mice-causes-alterations-in-dopamine-and-neurobehavioral-phenotypes-related-to-schizophrenia
#16
Francesca Managò, Maddalena Mereu, Surjeet Mastwal, Rosa Mastrogiacomo, Diego Scheggia, Marco Emanuele, Maria A De Luca, Daniel R Weinberger, Kuan Hong Wang, Francesco Papaleo
Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses...
August 23, 2016: Cell Reports
https://www.readbyqxmd.com/read/27501818/the-central-nervous-system-and-bone-metabolism-an-evolving-story
#17
REVIEW
Paul Dimitri, Cliff Rosen
Our understanding of the control of skeletal metabolism has undergone a dynamic shift in the last two decades, primarily driven by our understanding of energy metabolism. Evidence demonstrating that leptin not only influences bone cells directly, but that it also plays a pivotal role in controlling bone mass centrally, opened up an investigative process that has changed the way in which skeletal metabolism is now perceived. Other central regulators of bone metabolism have since been identified including neuropeptide Y (NPY), serotonin, endocannabinoids, cocaine- and amphetamine-regulated transcript (CART), adiponectin, melatonin and neuromedin U, controlling osteoblast and osteoclast differentiation, proliferation and function...
May 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/27441217/impaired-mtorc2-signaling-in-catecholaminergic-neurons-exaggerates-high-fat-diet-induced-hyperphagia
#18
Olga I Dadalko, Kevin Niswender, Aurelio Galli
OBJECTIVE: Food intake is highly regulated by central homeostatic and hedonic mechanisms in response to peripheral and environmental cues. Neutral energy balance stems from proper integration of homeostatic signals with those "sensing" the rewarding properties of food. Impairments in brain insulin signaling causes dysregulation of feeding behaviors and, as a consequence, hyperphagia. Here, we sought to determine how the mammalian target of rapamycin complex 2 (mTORC2), a complex involved in insulin signaling, influences high fat feeding...
September 2015: Heliyon
https://www.readbyqxmd.com/read/27419218/mesocortical-dopamine-phenotypes-in-mice-lacking-the-sonic-hedgehog-receptor-cdon
#19
Michael Verwey, Alanna Grant, Nicholas Meti, Lauren Adye-White, Angelica Torres-Berrío, Veronique Rioux, Martin Lévesque, Frederic Charron, Cecilia Flores
Motivated behaviors and many psychopathologies typically involve changes in dopamine release from the projections of the ventral tegmental area (VTA) and/or the substantia nigra pars compacta (SNc). The morphogen Sonic Hedgehog (Shh) specifies fates of midbrain dopamine neurons, but VTA-specific effects of Shh signaling are also being uncovered. In this study, we assessed the role of the Shh receptor Cdon in the development of VTA and SNc dopamine neurons. We find that Cdon is expressed in the proliferating progenitor zone of the embryonic ventral midbrain and that the number of proliferating cells in this region is increased in mouse Cdon(-/-) embryos...
May 2016: ENeuro
https://www.readbyqxmd.com/read/27404570/decreased-caffeine-induced-locomotor-activity-via-microinjection-of-cart-peptide-into-the-nucleus-accumbens-is-linked-to-inhibition-of-the-pcamkiia-d3r-interaction
#20
Qiang Fu, Xiaoyan Zhou, Yun Dong, Yonghong Huang, Jianhua Yang, Ki-Wan Oh, Zhenzhen Hu
The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 μM/0.5 μl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons...
2016: PloS One
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