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https://www.readbyqxmd.com/read/29776015/delta-9-tetrahydrocannabinol-potentiates-fear-memory-salience-through-functional-modulation-of-mesolimbic-dopaminergic-activity-states
#1
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
#2
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/29774428/inter-individual-differences-in-serotonin-and-glutamate-co-transmission-reflect-differentiation-in-context-induced-conditioned-50-khz-usvs-response-after-morphine-withdrawal
#3
Adam Hamed, Miron Bartosz Kursa
A growing body of research provides compelling evidence that in rats 50-kHz USVs are a form of expression of positive emotions. Context-induced 50-kHz USVs emission is variable among rats, indicating individual differences in contextual response bound up with pharmacological reward. The aims of this study were to: extract the most important neurotransmitters related to context-induced conditioned 50-kHz USVs response; find biological basis of existing inter-individual differences in context-induced conditioned 50-kHz USVs response; create a model of all-to-all neurotransmitters correlations...
May 17, 2018: Brain Structure & Function
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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/29748178/prognostic-significance-of-the-sodium-channel-blocker-test-in-patients-with-brugada-syndrome
#11
Akira Ueoka, Hiroshi Morita, Atsuyuki Watanabe, Yoshimasa Morimoto, Satoshi Kawada, Motomi Tachibana, Masakazu Miyamoto, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Ito
BACKGROUND: A drug provocation test using a sodium channel blocker (SCB) can unmask a type 1 ECG pattern in patients with Brugada syndrome. However, the prognostic value of the results of an SCB challenge is limited in patients with non-type 1 ECG. We investigated the associations of future risk for ventricular fibrillation with SCB-induced ECG changes and ventricular tachyarrhythmias (VTAs). METHODS AND RESULTS: We administered intravenous pilsicainide to 245 consecutive patients with Brugada syndrome (181 patients with spontaneous type 1 ECG, 64 patients with non-type 1 ECG)...
May 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29733459/hiv-1-tat-regulation-of-dopamine-transmission-and-microglial-reactivity-is-brain-region-specific
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/29727729/an-alarm-pheromone-reduces-ventral-tegmental-area-nucleus-accumbens-shell-responsivity
#16
Ana G Gutiérrez-García, Carlos M Contreras, Mauricio Saldivar-Lara
2-Heptanone (methyl n-amyl ketone) is a ketone that produces alarm reactions in insects (e.g., bees and ants). As an olfactory stimulus, 2-heptanone produces anxiety reactions in the short term and despair in the long term in rodent models. Among the anatomical connections of the olfactory system that integrate behavioral responses, connections between the amygdala and nucleus accumbens are important, which in turn form a circuit with the ventral tegmental area (VTA). 2-Heptanone increases the firing rate of amygdala neurons without participation of the vomeronasal organ...
May 1, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29723641/contributions-of-dopaminergic-and-non-dopaminergic-neurons-to-vta-stimulation-induced-neurovascular-responses-in-brain-reward-circuits
#17
Marta Brocka, Cornelia Helbing, Daniel Vincenz, Thomas Scherf, Dirk Montag, Jürgen Goldschmidt, Frank Angenstein, Michael Lippert
Mapping the activity of the human mesolimbic dopamine system by BOLD-fMRI is a tempting approach to non-invasively study the action of the brain reward system during different experimental conditions. However, the contribution of dopamine release to the BOLD signal is disputed. To assign the actual contribution of dopaminergic and non-dopaminergic VTA neurons to the formation of BOLD responses in target regions of the mesolimbic system, we used two optogenetic approaches in rats. We either activated VTA dopaminergic neurons selectively, or dopaminergic and mainly glutamatergic projecting neurons together...
April 30, 2018: NeuroImage
https://www.readbyqxmd.com/read/29715476/epigenetic-upregulation-of-cxcl12-expression-contributes-to-the-acquisition-and-maintenance-of-morphine-induced-conditioned-place-preference
#18
Huan Liu, Jiayou Wei, Meng Liu, Shaoling Wu, Chao Ma, Cuicui Liu, Kangmei Huang, Xueqin Zhang, Ruixian Guo, Kuibo Zhang, Wenjun Xin
Addiction and rewarding effect is a primary side effect of morphine, which is commonly used to relieve the acute or chronic pain. Several lines of evidence have suggested that inflammation response in the VTA contributes to morphine-induced reward (conditioned place preference, CPP), while the mechanism are poorly understood. The present study showed that repeated morphine conditioning persistently increased the expression of CXCL12 mRNA and protein in VTA. Furthermore, inhibition of CXCL12 prevented the acquisition and maintenance, but not the expression, of morphine-induced CPP in rodent...
April 30, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29712788/mesocorticolimbic-connectivity-and-volumetric-alterations-in-dcc-mutation-carriers
#19
Daniel E Vosberg, Yu Zhang, Aurore Menegaux, Amanda Chalupa, Colleen Manitt, Simone Zehntner, Conrad Eng, Kristina DeDuck, Dominique Allard, France Durand, Alain Dagher, Chawki Benkelfat, Myriam Srour, Ridha Joober, Franco Lepore, Guy Rouleau, Hugo Théoret, Barry J Bedell, Cecilia Flores, Marco Leyton
The axon guidance cue receptor DCC plays a critical role in the organization of mesocorticolimbic pathways in rodents. To investigate whether this occurs in humans, we measured (i) anatomical connectivity between the ventral tegmental area/substantia nigra (SN/VTA) and forebrain targets, (ii) striatal and cortical volumes, and (iii) putatively associated traits and behaviors. To assess translatability, morphometric data were also collected in Dcc haploinsufficient mice.The human volunteers were 20 DCC +/- mutation carriers, 16 DCC +/+ relatives, and 20 DCC +/+ unrelated healthy volunteers (UHV) (28 females)...
April 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29704516/the-neuroanatomic-complexity-of-the-crf-and-da-systems-and-their-interface-what-we-still-don-t-know
#20
REVIEW
E A Kelly, J L Fudge
Corticotropin-releasing factor (CRF) is a neuropeptide that mediates the stress response. Long known to contribute to regulation of the adrenal stress response initiated in the hypothalamic-pituitary axis (HPA), a complex pattern of extrahypothalamic CRF expression is also described in rodents and primates. Cross-talk between the CRF and midbrain dopamine (DA) systems links the stress response to DA regulation. Classically CRF+ cells in the extended amygdala and paraventricular nucleus (PVN) are considered the main source of this input, principally targeting the ventral tegmental area (VTA)...
April 25, 2018: Neuroscience and Biobehavioral Reviews
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