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ventral tegmental area (VTA)

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https://www.readbyqxmd.com/read/29785351/genetic-inactivation-of-alpha-synuclein-affects-embryonic-development-of-dopaminergic-neurons-of-the-substantia-nigra-but-not-the-ventral-tegmental-area-in-mouse-brain
#1
Tatiana V Tarasova, Olga A Lytkina, Valeria V Goloborshcheva, Larisa N Skuratovskaya, Alexandr I Antohin, Ruslan K Ovchinnikov, Michail S Kukharsky
Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration...
2018: PeerJ
https://www.readbyqxmd.com/read/29782882/prolonged-increase-in-ser31-tyrosine-hydroxylase-phosphorylation-in-substantia-nigra-following-cessation-of-chronic-methamphetamine
#2
Michael F Salvatore, Vicki A Nejtek, Habibeh Khoshbouei
Methamphetamine (MA) exposure may increase the risk of motor or cognitive impairments similar to Parkinson's disease (PD) by middle age. Although damage to nigrostriatal or mesoaccumbens dopamine (DA) neurons may occur during or early after MA exposure, overt PD-like symptoms at a younger age may not manifest due to compensatory mechanisms to maintain DA neurotransmission. One possible compensatory mechanism is increased tyrosine hydroxylase (TH) phosphorylation. In the rodent PD 6-OHDA model, nigrostriatal lesion decreases TH protein in both striatum and substantia nigra (SN)...
May 18, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29782623/astrocytic-hypertrophy-in-the-rat-ventral-tegmental-area-following-chronic-morphine-differs-with-age
#3
Emily C Goins, Dusica Bajic
The ventral tegmental area (VTA) is the origin of the mesolimbic dopaminergic system known to play an integral role in mediating reward and development of drug addiction. Although the differences in neuronal plasticity of VTA at various ages remain to be understood, age is known to influence the effects of chronic opioids. In addition, adaptations associated with exposure to opioids within glial populations located in the VTA are poorly understood. The objective of the study was to determine if there are changes in astrocytic immunofluorescent labeling in the VTA following chronic morphine administration in a rat model at different ages: newborn at postnatal day (PD)7 and adult (estimated PD57)...
2018: Journal of neurology and neurorehabilitation research
https://www.readbyqxmd.com/read/29781560/conditioned-reward-of-opioids-but-not-psychostimulants-is-impaired-in-gaba-a-receptor-%C3%AE-subunit-knockout-mice
#4
Milo S Siivonen, Elena de Miguel, Juho Aaltio, Aino K Manner, Mikko Vahermo, Jari Yli-Kauhaluoma, Anni-Maija Linden, Teemu Aitta-Aho, Esa R Korpi
Extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ-GABAA Rs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA-site agonist gaboxadol and neuroactive steroids. Among other regions, these δ-GABAA Rs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviors, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ-GABAA R knockout mice (δ-KO)...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29780881/nucleus-accumbens-microcircuit-underlying-d2-msn-driven-increase-in-motivation
#5
Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, Ana João Rodrigues
The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29778899/dopamine-loss-alters-the-hippocampus-nucleus-accumbens-synaptic-transmission-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#6
Alberto Cordella, Paraskevi Krashia, Annalisa Nobili, Annabella Pignataro, Livia La Barbera, Maria Teresa Viscomi, Alessandro Valzania, Flavio Keller, Martine Ammassari-Teule, Nicola Biagio Mercuri, Nicola Berretta, Marcello D'Amelio
The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD...
May 17, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29778509/longitudinal-observations-using-simultaneous-fmri-multiple-channel-electrophysiology-recording-and-chemical-microiontophoresis-in-the-rat-brain
#7
Saul Jaime, Jose E Cavazos, Yihong Yang, Hanbing Lu
BACKGROUND: fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. NEW METHODS: Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months...
May 17, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29776015/delta-9-tetrahydrocannabinol-potentiates-fear-memory-salience-through-functional-modulation-of-mesolimbic-dopaminergic-activity-states
#8
Aurelie Fitoussi, Jordan Zunder, Huibing Tan, Steven R Laviolette
Chronic or acute exposure to delta-9-tetrahydrocannabinol (THC), the main psychoactive compound in cannabis, has been associated with numerous neuropsychiatric side-effects, including dysregulation of emotional processing and associative memory formation. Clinical and pre-clinical evidence suggests that the effects of THC are due to the ability to modulate mesolimbic dopamine (DA) activity states in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Nevertheless, the mechanisms by which THC modulates mesolimbic DA function and emotional processing are not well understood...
May 18, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29775679/identification-and-validation-of-midbrain-kcnq4-regulation-of-heavy-alcohol-consumption-in-rodents
#9
Natalie S McGuier, Jennifer A Rinker, Reginald Cannady, Diana B Fulmer, Sara R Jones, Michaela Hoffman, Patrick J Mulholland
Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode KV 7 channels influence alcohol intake and dependence. KV 7 channels are a class of slowly activating voltage-dependent K+ channels that regulate neuronal excitability. Studies indicate that the KV 7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29773910/the-l-type-calcium-channel-blocker-isradipine-attenuates-cue-induced-cocaine-seeking-by-enhancing-dopaminergic-activity-in-the-ventral-tegmental-area-to-nucleus-accumbens-pathway
#10
Nii A Addy, Eric J Nunes, Shannon M Hughley, Keri M Small, Sarah J Baracz, Joshua L Haight, Anjali M Rajadhyaksha
Previous preclinical and clinical investigations have focused on the L-type calcium channel (LTCC) as a potential therapeutic target for substance abuse. While some clinical studies have examined the ability of LTCC blockers to alter cocaine's subjective effects, very few LTCC studies have examined cocaine relapse. Here, we examined whether ventral tegmental area (VTA)-specific or systemic administration of the LTCC inhibitor, isradipine, altered cocaine-seeking behavior in a rat model. Male Sprague-Dawley rats first received 10 days of cocaine self-administration training (2 h sessions), where active lever depression resulted in delivery of a ∼0...
May 3, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29773830/circadian-and-homeostatic-modulation-of-multi-unit-activity-in-midbrain-dopaminergic-structures
#11
Karim Fifel, Johanna H Meijer, Tom Deboer
Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29770121/overexpression-of-thioredoxin-1-blocks-morphine-induced-conditioned-place-preference-through-regulating-the-interaction-of-%C3%AE-aminobutyric-acid-and-dopamine-systems
#12
Xiang Li, Mengbing Huang, Lihua Yang, Ningning Guo, Xiaoyan Yang, Zhimin Zhang, Ming Bai, Lu Ge, Xiaoshuang Zhou, Ye Li, Jie Bai
Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29766048/phasic-stimulation-of-midbrain-dopamine-neuron-activity-reduces-salt-consumption
#13
Eleanor C Sandhu, Anushka B P Fernando, Elaine E Irvine, Kyoko Tossell, Michelle Kokkinou, Justyna Glegola, Mark A Smith, Oliver D Howes, Dominic J Withers, Mark A Ungless
Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviors, has been implicated. We, therefore, examined the effects on salt consumption of either optogenetic excitation or chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons in male mice...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29760181/corticosterone-signaling-and-a-lateral-habenula-ventral-tegmental-area-circuit-modulate-compulsive-self-injurious-behavior-in-a-rat-model
#14
Yujie Guo, Xun Tang, Jichuan Zhang, Sen Jin, Jinnan Li, Lufeng Ding, Keming Zhang, Chaoyu Yang, Hua Zhou, Xiaobin He, Fuqiang Xu, Guo-Qiang Bi, Lin Xu, Pak-Ming Lau
Self-injurious behavior (SIB) is commonly observed in patients with neuropsychiatric disorders, as well as nonclinical populations with stress related mental health problems. However, the exact circuitry mechanisms underlying SIB have remained unclear. Here we established a rat model of SIB with bilateral injection of muscimol into entopeduncular nucleus (EP). Following the muscimol injection, the male rats exhibited stereotypic self-biting behavior that lasted for hours and often resulted in wounds of various severities, in a dose-dependent manner...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29753648/nicotinamide-phosphoribosyltransferase-regulates-cocaine-reward-through-sirtuin-1
#15
Jueying Kong, Changman Du, Linhong Jiang, Wei Jiang, Pengchi Deng, Xue Shao, Baolai Zhang, Yan Li, Ruiming Zhu, Qian Zhao, Dengqi Fu, Hui Gu, Li Luo, Hailei Long, Yinglan Zhao, Xiaobo Cen
Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) biosynthesis in mammals, converts nicotinamide into nicotinamide mononucleotide (NMN). NMN is subsequently converted to NAD, a component that is critical for cell energy metabolism and survival. Sirtuin 1 (SIRT1), an NAD-dependent histone deacetylase, plays an important role in mediating memory and synaptic plasticity. Here, we found that NAMPT was significantly upregulated in the ventral tegmental area (VTA) of cocaine-conditioned mice...
May 10, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29751760/regional-microglia-are-transcriptionally-distinct-but-similarly-exacerbate-neurodegeneration-in-a-culture-model-of-parkinson-s-disease
#16
Eric Wildon Kostuk, Jingli Cai, Lorraine Iacovitti
BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP+ )...
May 11, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29733459/hiv-1-tat-regulation-of-dopamine-transmission-and-microglial-reactivity-is-brain-region-specific
#17
Douglas R Miller, Fatemeh Shaerzadeh, Leah Phan, Nesrin Sharif, Joyonna Gamble-George, Jay P McLaughlin, Wolfgang J Streit, Habibeh Khoshbouei
The transactivator of transcription protein, HIV-1 Tat, is linked to neuroAIDS, where degeneration of dopamine neurons occurs. Using a mouse model expressing GFAP-driven Tat protein under doxycycline (Dox) regulation, we investigated microglial-neuronal interactions in the rostral substantia nigra pars compacta (SNc). Immunohistochemistry for microglia and tyrosine hydroxylase (TH) showed that the ratio of microglia to dopamine neurons is smaller in the SNc than in the ventral tegmental area (VTA) and that this difference is maintained following 7-day Dox exposure in wild type animals...
May 7, 2018: Glia
https://www.readbyqxmd.com/read/29729221/could-gaba-with-a-side-of-glycine-control-glutamate-receptors
#18
Salma A Quraishi, Carlos A Paladini
Dopamine neurons within the ventral tegmental area (VTA) synthesize diverse sources of inhibition and excitation to generate precise signals that underlie reward and aversion. Multiple lines of evidence point to the dominant influence of inhibition of dopamine neurons. The majority of synapses they receive are GABAergic (Bolam & Smith, 1990; Henny et al., 2012); they sustain persistent IPSPs in vivo (Grace & Bunney, 1985); and GABA receptor-mediated inhibition supersedes glutamatergic excitation to control firing pattern (Lobb et al...
May 5, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29729086/the-novel-atypical-antipsychotic-cariprazine-demonstrates-dopamine-d-2-receptor-dependent-partial-agonist-actions-on-rat-mesencephalic-dopamine-neuronal-activity
#19
Sarah Delcourte, Charles R Ashby, Renaud Rovera, Béla Kiss, Nika Adham, Bence Farkas, Nasser Haddjeri
AIM: Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). METHODS: Extracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907...
May 4, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29728703/nad-cellular-redox-and-sirt1-regulate-the-diurnal-rhythms-of-tyrosine-hydroxylase-and-conditioned-cocaine-reward
#20
Ryan W Logan, Puja K Parekh, Gabrielle N Kaplan, Darius D Becker-Krail, Wilbur P Williams, Shintaro Yamaguchi, Jun Yoshino, Micah A Shelton, Xiyu Zhu, Hui Zhang, Spencer Waplinger, Ethan Fitzgerald, Jeffrey Oliver-Smith, Poornima Sundarvelu, John F Enwright, Yanhua H Huang, Colleen A McClung
The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration...
May 4, 2018: Molecular Psychiatry
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