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Ishan Gupta, Andrew M J Young
The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release...
March 7, 2018: Brain Research
Yuan-Hao Chen, Tung-Tai Kuo, Eagle Yi-Kung Huang, Yu-Ching Chou, Yung-Hsiao Chiang, Barry J Hoffer, Jonathon Miller
Background: Traumatic brain injury is associated with substantial alterations in reward processing, but underlying mechanisms are controversial. Objective: A better understanding of alterations in dopamine (DA) release patterns from the dorsal striatum and nucleus accumbens shell (NAc) may provide insights into posttraumatic reward pathology. Materials and Methods: The patterns of DA release with or without exposure to nicotine in brain slices with striatum and NAc, isolated from Sprague-Dawley rats with 6 psi fluid percussion (FPI) or sham injury were analysis by using fast-scan cyclic voltammetry...
February 9, 2018: Oncotarget
Josué O Suárez-Ortiz, Felipe Cortés-Salazar, Ariadna L Malagón-Carrillo, Verónica E López-Alonso, Juan M Mancilla-Díaz, Juan G Tejas-Juárez, Rodrigo E Escartín-Pérez
Overeating is one of the most relevant clinical features in Binge Eating Disorder and in some obesity patients. According to several studies, alterations in the mesolimbic dopaminergic transmission produced by non-homeostatic feeding behavior may be associated with changes in the reward system similar to those produced by drugs of abuse. Although it is known that binge-eating is related with changes in dopaminergic transmission mediated by D2 receptors in the nucleus accumbens shell (NAcS), it has not been determined whether these receptors may be a potential target for the treatment of eating pathology with binge-eating...
2018: Frontiers in Neuroscience
Ritchy Hodebourg, Jennifer E Murray, Maxime Fouyssac, Mickaël Puaud, Barry J Everitt, David Belin
The alarming increase in heroin overdoses in the USA is a reminder of the need for efficacious and novel treatments for opiate addiction. This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behavior. While cocaine reinforcement depends on the mesolimbic system, well established cocaine seeking is dependent on dorsolateral striatum (aDLS) dopamine-dependent mechanisms which are disrupted by N-acetylcysteine, through normalisation of corticostriatal glutamate homeostasis...
March 7, 2018: European Journal of Neuroscience
Adam J Stark, Christopher T Smith, Ya-Chen Lin, Kalen J Petersen, Paula Trujillo, Nelleke C van Wouwe, Hakmook Kang, Manus J Donahue, Robert M Kessler, David H Zald, Daniel O Claassen
The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D2 -like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population...
February 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Deena M Walker, Eric J Nestler
Drug addiction involves long-term behavioral abnormalities that arise in response to repeated exposure to drugs of abuse in vulnerable individuals. It is a multifactorial syndrome involving a complex interplay between genes and the environment. Evidence suggests that the underlying mechanisms regulating these persistent behavioral abnormalities involve changes in gene expression throughout the brain's reward circuitry, in particular, in the mesolimbic dopamine system. In the past decade, investigations have begun to reveal potential genes involved in the risk for addiction through genomewide association studies...
2018: Handbook of Clinical Neurology
Charles S Bockman, Wanyun Zeng, Jamie Hall, Beth Mittelstet, Liz Schwarzkopf, Dustin J Stairs
RATIONALE: Individuals vary in sensitivity to the behavioral effects of nicotine, resulting in differences in vulnerability to nicotine addiction. The role of rearing environment in determining individual sensitivity to nicotine is unclear. The neuropharmacological mechanisms mediating the effect of rearing environment on the behavioral actions of nicotine are also poorly understood. OBJECTIVES: The contribution of rearing environment in determining the sensitivity to the interoceptive effects of nicotine was determined in rats reared in isolated conditions (IC) or enriched conditions (EC)...
February 21, 2018: Psychopharmacology
Hillary L Woodworth, Patricia A Perez-Bonilla, Bethany G Beekly, Trevor J Lewis, Gina M Leinninger
Neurotensin (Nts) promotes activation of dopamine (DA) neurons in the ventral tegmental area (VTA) via incompletely understood mechanisms. Nts can signal via the G protein-coupled Nts receptors 1 and 2 (NtsR1 and NtsR2), but the lack of methods to detect NtsR1- and NtsR2-expressing cells has limited mechanistic understanding of Nts action. To overcome this challenge, we generated dual recombinase mice that express FlpO-dependent Cre recombinase in NtsR1 or NtsR2 cells. This strategy permitted temporal control over recombination, such that we could identify NtsR1- or NtsR2-expressing cells and determine whether their distributions differed between the developing and adult brain...
January 2018: ENeuro
Andrea Stojakovic, Magdalena Walczak, Przemysław E Cieślak, Aleksandra Trenk, Johan Sköld, Joanna Zajdel, Elahe Mirrasekhian, Camilla Karlsson, Annika Thorsell, Markus Heilig, Jan Rodriguez Parkitna, Tomasz Błasiak, David Engblom
The risk factors for developing alcohol addiction include impulsivity, high sensitivity to the rewarding action of ethanol, and low sensitivity to its sedative and intoxicating effects. Genetic variation in GABAA receptor subunits, including the ɣ2 subunit (Gabrg2), affects the risk for developing alcoholism. Alcohol directly potentiates GABAA receptors and activates the mesolimbic dopamine system. Here, we deleted Gabrg2 selectively in dopamine cells of adult mice. The deletion resulted in elevated firing of dopamine neurons and made them less sensitive to drugs acting at GABAA receptors...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
K László, L Péczely, A Kovács, O Zagoracz, T Ollmann, E Kertes, V Kállai, B Csetényi, Z Karádi, L Lénárd
Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test...
February 17, 2018: Behavioural Brain Research
Rafael N Ruggiero, Matheus T Rossignoli, Cleiton Lopes-Aguiar, João P Leite, Lezio S Bueno-Junior, Rodrigo N Romcy-Pereira
Mood disorders are associated to functional unbalance in mesolimbic and frontal cortical circuits. As a commonly used mood stabilizer, lithium acts through multiple biochemical pathways, including those activated by muscarinic cholinergic receptors crucial for hippocampal-prefrontal communication. Therefore, here we investigated the effects of lithium on prefrontal cortex responses under cholinergic drive. Lithium-treated rats were anesthetized with urethane and implanted with a ventricular cannula for muscarinic activation, a recording electrode in the medial prefrontal cortex (mPFC), and a stimulating electrode in the intermediate hippocampal CA1...
February 16, 2018: Experimental Neurology
Dana Mayer, Evelyn Kahl, Taygun C Uzuneser, Markus Fendt
The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
J C Klein, M Rolinski, L Griffanti, K Szewczyk-Krolikowski, F Baig, C Ruffmann, A R Groves, R A L Menke, M T Hu, C Mackay
Magnetic resonance imaging (MRI) studies in early Parkinson's disease (PD) have shown promise in the detection of disease-related brain changes in the white and deep grey matter. We set out to establish whether intrinsic cortical involvement in early PD can be detected with quantitative MRI. We collected a rich, multi-modal dataset, including diffusion MRI, T1 relaxometry and cortical morphometry, in 20 patients with early PD (disease duration, 1.9 ± 0.97 years, Hoehn & Yahr 1-2) and in 19 matched controls...
February 13, 2018: NMR in Biomedicine
Sarah-Jane Leigh, Frances Lee, Margaret J Morris
PURPOSE OF REVIEW: This review investigates how exposure to palatable food and its associated cues alters appetite regulation and feeding behaviour to drive overeating and weight gain. RECENT FINDINGS: Both supraphysiological and physiological feeding systems are affected by exposure to palatable foods and its associated cues. Preclinical research, largely using rodents, has demonstrated that palatable food modulates feeding-related neural systems and food-seeking behaviour by recruiting the mesolimbic reward pathway...
February 13, 2018: Current Obesity Reports
Sarah M Tashjian, Adriana Galván
The 2016 U.S. presidential election yielded distress among many individuals who identify with historically marginalized groups. We used functional magnetic resonance imaging (fMRI) and psychological measures to test the hypotheses that neural response to reward, probing the nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), and social support would ameliorate the effects of election distress among those who felt negatively affected by the result. Within four months of the 2016 U.S. presidential election, we tested human participants who felt affected by the election result (N = 40, Mage = 21...
February 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
James K Rilling, Xiangchuan Chen, Xu Chen, Ebrahim Haroon
Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model...
February 10, 2018: American Journal of Primatology
Paul M Klenowski, Andrew R Tapper
Ethanol and nicotine can modulate the activity of several neurotransmitter systems and signalling pathways. Interactions between ethanol and nicotine can also occur via common molecular targets including nicotinic acetylcholine receptors (nAChRs). These effects can induce molecular and synaptic adaptations that over time, are consolidated in brain circuits that reinforce drug-seeking behavior, contribute to the development of withdrawal symptoms during abstinence and increase the susceptibility to relapse. This chapter will discuss the acute and chronic effects of ethanol and nicotine within the mesolimbic reward pathway and brain circuits involved in learning, memory, and withdrawal...
February 9, 2018: Handbook of Experimental Pharmacology
Clarissa M Liu, Scott E Kanoski
Understanding the neurobiological controls of feeding behavior is critical in light of the growing obesity pandemic, a phenomenon largely based on excessive caloric consumption. Feeding behavior and its underlying biological substrates are frequently divided in the literature into two separate categories: [1] homeostatic processes involving energy intake based on caloric and other metabolic deficits, and [2] non-homeostatic processes that involve feeding driven by environmental and cognitive factors. The present review summarizes both historic and recent research examining the homeostatic regulation of feeding with specific emphasis on hypothalamic and hindbrain circuitry that monitor and regulate various metabolic signals...
February 5, 2018: Physiology & Behavior
Laura López-Cruz, Noemí San Miguel, Carla Carratalá-Ros, Lidón Monferrer, John D Salamone, Mercè Correa
The mesolimbic dopamine (DA) system plays a critical role in behavioral activation and effort-based decision-making. DA depletion produces anergia (shifts to low effort options) in animals tested on effort-based decision-making tasks. Caffeine, the most consumed stimulant in the world, acts as an adenosine A1 /A2A receptor antagonist, and in striatal areas DA D1 and D2 receptors are co-localized with adenosine A1 and A2A receptors respectively. In the present work, we evaluated the effect of caffeine on anergia induced by the VMAT-2 inhibitor tetrabenazine (TBZ), which depletes DA...
February 2, 2018: Neuropharmacology
Marcela Ferreño, Natalia Uriarte, María José Zuluaga, Annabel Ferreira, Daniella Agrati
Pups have greater incentive value than males for rats during the postpartum estrus (PPE); a period when females are both maternally and sexually motivated. Mesolimbic dopaminergic system has been proposed as a general motivational circuit; however in the literature it has been more related to the control of the motivational aspects of maternal than sexual motivations of females. Therefore, we aimed to assess the effect of antagonizing dopaminergic neurotransmission of PPE females on their preference for pups over a male...
February 2, 2018: Physiology & Behavior
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