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norepinephrine and accumbens

Jin W Park, Rohan V Bhimani, Jinwoo Park
Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlying mechanisms of how LC-NE regulates DA transmission via VTA-DA neurons remain largely unexplored. Herein, we investigated how electrical stimulation of the LC modulates VTA-DA neurotransmission in the nucleus accumbens (NAc)...
June 21, 2017: ACS Chemical Neuroscience
Wenli Mi, Shuxing Wang, Zerong You, Grewo Lim, Michael F McCabe, Hyangin Kim, Lucy Chen, Jianren Mao
BACKGROUND: Combination drug therapy is commonly used to treat chronic pain conditions such as neuropathic pain, and antidepressant is often used together with opioid analgesics. While rewarding is an intrinsic property of opioid analgesics, it is unknown whether the use of an antidepressant would influence opioid reward, which may contribute to opioid addiction. In this study, we examined whether nortriptyline (a tricyclic antidepressant and a first-line medication for neuropathic pain) would enhance the morphine rewarding property in both naive and chronic constriction sciatic nerve injury (CCI) rats...
May 19, 2017: Anesthesia and Analgesia
Serena A Allen, Stephanie Rednour, Samantha Shepard, Brooks Barnes Pond
A rapid, sensitive, and reproducible assay is described for the quantitative determination of the monoamine neurotransmitters dopamine, norepinephrine and serotonin, their metabolites, and the internal standard 3,4-dihydroxybenzlyamine hydro-bromide in mouse brain homogenate using high-performance liquid chromatography with electrochemical detection. The method was validated in the following brain areas: frontal cortex, striatum, nucleus accumbens, hippocampus, substantia nigra pars compacta and ventral tegmental area...
May 5, 2017: Biomedical Chromatography: BMC
Karl T Schmidt, Jason P Schroeder, Stephanie L Foster, Katherine Squires, Brilee M Smith, Elizabeth G Pitts, Michael P Epstein, David Weinshenker
Drug-primed reinstatement of cocaine seeking in rats is thought to reflect relapse-like behavior and is mediated by the integration of signals from mesocorticolimbic dopaminergic projections and corticostriatal glutamatergic innervation. Cocaine-primed reinstatement can also be attenuated by systemic administration of dopamine β-hydroxylase (DBH) inhibitors, which prevent norepinephrine (NE) synthesis, or by α1-adrenergic receptor (α1AR) antagonists, indicating functional modulation by the noradrenergic system...
June 2017: Neuropharmacology
David J Mokler, Christine E Miller, Jill A McGaughy
Adolescence is a period during which many aspects of executive function are maturing. Much of the literature has focused on discrepancies between sub-cortical and cortical development that is hypothesized to lead to over-processing of reinforcement related stimuli unchecked by fully matured response inhibition. Specifically, maturation of sub-cortical dopaminergic systems that terminate in the nucleus accumbens has been suggested to occur prior to the full maturation of corticopetal dopaminergic systems. However, converging evidence supports the hypothesis that many aspects of cognitive control are critically linked to cortical noradrenergic systems, that the effectiveness of drugs used to treat disorders of executive function, e...
February 17, 2017: Neurobiology of Learning and Memory
S Mechiel Korte, Jolanda Prins, Filip S Van den Bergh, Ronald S Oosting, Rudy Dupree, Gerdien A H Korte-Bouws, Koen G C Westphal, Berend Olivier, Damiaan A Denys, Alexis Garland, Onur Güntürkün
The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward...
January 5, 2017: European Journal of Pharmacology
Eric Murillo-Rodríguez, Khalil Guzmán, Gloria Arankowsky-Sandoval, Mireille Salas-Crisóstomo, Ramsés Jiménez-Moreno, Oscar Arias-Carrión
The peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily that has been suggested as a modulator of several physiological functions. The PPARα recognizes as an endogenous ligand the anorexic lipid mediator oleoylethanolamide (OEA) which displays wake-inducing properties. Despite that recent evidence indicates that activation of PPARα by synthetic agonists such as Wy14643 enhances waking as well as the extracellular contents of wake-related neurotransmitters, the role of PPARα in sleep recovery after prolonged waking has not been fully described...
September 16, 2016: Brain Research Bulletin
M F Lazenka, J A Suyama, C T Bauer, M L Banks, S S Negus
3,4-Methylenedioxymethamphetamine (MDMA) is a substrate for dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse-related MDMA effects, the present study compared MDMA effects on intracranial self-stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague-Dawley rats...
January 2017: Pharmacology, Biochemistry, and Behavior
Adem Can, Panos Zanos, Ruin Moaddel, Hye Jin Kang, Katinia S S Dossou, Irving W Wainer, Joseph F Cheer, Douglas O Frost, Xi-Ping Huang, Todd D Gould
Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine's antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine's side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system...
October 2016: Journal of Pharmacology and Experimental Therapeutics
Megan E Fox, Nathan T Rodeberg, R Mark Wightman
Dysregulated catecholamine signaling has long been implicated in drug abuse. Although much is known about adaptations following chronic drug administration, little work has investigated how a single drug exposure paired with withdrawal influences catecholamine signaling in vivo. We used fast-scan cyclic voltammetry in freely moving rats to measure real-time catecholamine overflow during acute morphine exposure and naloxone-precipitated withdrawal in two regions associated with the addiction cycle: the dopamine-dense nucleus accumbens (NAc) and norepinephrine-rich ventral bed nucleus of the stria terminalis (vBNST)...
February 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Christopher Fitzpatrick, Justin F Creeden, Shane A Perrine, Jonathan D Morrow
Individual variation in the attribution of motivational salience to reward-related cues is believed to underlie addiction vulnerability. Pavlovian conditioned approach measures individual variation in motivational salience by identifying rats that are attracted to and motivated by reward cues (sign-trackers) or motivationally fixed on the reward itself (goal-trackers). Previously, it has been demonstrated that sign-trackers are more vulnerable to addiction-like behavior. Moreover, sign-trackers release more dopamine in the nucleus accumbens than goal-trackers in response to reward-related cues, and sign- but not goal-tracking behavior is dopamine-dependent...
July 20, 2016: Hippocampus
F P Mayer, L Wimmer, O Dillon-Carter, J S Partilla, N V Burchardt, M D Mihovilovic, M H Baumann, H H Sitte
BACKGROUND AND PURPOSE: 4-Methyl-N-methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate-type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5-HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N-demethylated metabolite, 4-methylcathinone (nor-mephedrone); the ring-hydroxylated metabolite, 4-hydroxytolylmephedrone (4-OH-mephedrone); and the reduced keto-metabolite, dihydromephedrone. EXPERIMENTAL APPROACH: We used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter-mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes...
September 2016: British Journal of Pharmacology
Krishna G Seshadri
Romantic love could be considered as a collection of activities associated with the acquisition and retention of emotions needed to survive and reproduce. These emotions change the individual's behavioural strategies in a way that will increase the likelihood of achieving these goals. Love may be defined as an emergent property of an ancient cocktail of neuropeptides and neurotransmitters. It appears that lust, attachment and attraction appear to be distinct but intertwined processes in the brain each mediated by its own neurotransmitters and circuits...
July 2016: Indian Journal of Endocrinology and Metabolism
Samantha E Yohn, Emily E Errante, Aaron Rosenbloom-Snow, Matthew Somerville, Margaret Rowland, Kristin Tokarski, Nadia Zafar, Merce Correa, John D Salamone
Deficits in behavioral activation, exertion of effort, and other psychomotor/motivational symptoms are frequently seen in people with depression and other disorders. Depressed people show a decision bias towards selection of low effort activities, and animal tests of effort-related decision making are being used as models of motivational dysfunctions seen in psychopathology. The present studies investigated the ability of drugs that block dopamine transport (DAT), norepinephrine transport (NET), and serotonin transport (SERT) to modulate work output in rats responding on a test of effort-related decision making (i...
October 2016: Neuropharmacology
P L Naplekova, S V Shevchenko, V B Narkevich, T S Gan'shina, L M Kostochka, R S Mirzoyan, V S Kudrin, T A Voronina
The influence of perspective anti-migraine drug tropoxin on the content of monoamines and related metabolites in Wistar rat brain structures, including frontal cortex (FC), hypothalamus, nucleus accumbens (NA), striatum, and hippocampus, has been studied using HPLC/ED technique. Tropoxin (10 mg/kg) induced a 30% decrease (p < 0.05) in dopamine (DA) level in FC as well as norepinephrine content in NA, while the concentrations of DA metabolites DOPAC and HVA in the hypothalamus were found to increase. The injection of tropoxin in a dose of 20 mg/kg led to an increase in HVA level in hypothalamus as well as seroto- nin metabolite 5-HIAA content in NA...
2016: Eksperimental'naia i Klinicheskaia Farmakologiia
Amanda A Braun, Robyn M Amos-Kroohs, Arnold Gutierrez, Kerstin H Lundgren, Kim B Seroogy, Charles V Vorhees, Michael T Williams
The nucleus accumbens (Nacc) and medial prefrontal cortex (mPFC) receive dopaminergic innervation from the ventral tegmental area and are involved in learning. Male rats with 6-hydroxydopamine (6-OHDA)-induced dopaminergic and noradrenergic reductions in the Nacc or mPFC were tested for allocentric and egocentric learning to determine their role in these forms of neuroplasticity. mPFC dopaminergic and noradrenergic reductions did not result in changes to either type of learning or memory. Nacc dopaminergic and noradrenergic reductions resulted in allocentric learning and memory deficits in the Morris water maze (MWM) on acquisition, reversal, and probe trials...
August 2016: Neurotoxicity Research
Rama M Kamal, Martijn S van Noorden, Ernst Franzek, Boukje A G Dijkstra, Anton J M Loonen, Cornelius A J De Jong
OBJECTIVE: x03B3;-Hydroxybutyrate (GHB) has gained popularity as a drug of abuse. In the Netherlands the number of patients in treatment for GHB dependence has increased sharply. Clinical presentation of GHB withdrawal can be life threatening. We aim, through this overview, to explore the neurobiological pathways causing GHB dependency and withdrawal, and their implications for treatment choices. METHODS: In this work we review the literature discussing the findings from animal models to clinical studies focused on the neurobiological pathways of endogenous but mainly exogenous GHB...
2016: Neuropsychobiology
Alexander G Zestos, Sarah R Mikelman, Robert T Kennedy, Margaret E Gnegy
Amphetamine abuse afflicts over 13 million people, and there is currently no universally accepted treatment for amphetamine addiction. Amphetamine serves as a substrate for the dopamine transporter and reverses the transporter to cause an increase in extracellular dopamine. Activation of the beta subunit of protein kinase C (PKCβ) enhances extracellular dopamine in the presence of amphetamine by facilitating the reverse transport of dopamine and internalizing the D2 autoreceptor. We previously demonstrated that PKCβ inhibitors block amphetamine-stimulated dopamine efflux in synaptosomes from rat striatum in vitro...
June 15, 2016: ACS Chemical Neuroscience
Tatiana A Shnitko, Sarah C Taylor, Sierra J Stringfield, Shannon L Zandy, Roberto U Cofresí, James M Doherty, William B Lynch, Charlotte A Boettiger, Rueben A Gonzales, Donita L Robinson
RATIONALE: Dopamine plays a critical role in striatal and cortical function, and depletion of the dopamine precursors phenylalanine and tyrosine is used in humans to temporarily reduce dopamine and probe the role of dopamine in behavior. This method has been shown to alter addiction-related behaviors and cognitive functioning presumably by reducing dopamine transmission, but it is unclear what specific aspects of dopamine transmission are altered. OBJECTIVES: We performed this study to confirm that administration of an amino acid mixture omitting phenylalanine and tyrosine (Phe/Tyr[-]) reduces tyrosine tissue content in the prefrontal cortex (PFC) and nucleus accumbens (NAc), and to test the hypothesis that Phe/Tyr[-] administration reduces phasic dopamine release in the NAc...
June 2016: Psychopharmacology
Mohammed Abul Kashem, Selina Ahmed, Nilufa Sultana, Eakhlas U Ahmed, Russell Pickford, Caroline Rae, Omar Šerý, Iain S McGregor, Vladimir J Balcar
We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry...
February 2016: Neurochemical Research
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