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https://www.readbyqxmd.com/read/28324454/reward-circuitry-in-addiction
#1
REVIEW
Sarah Cooper, A J Robison, Michelle S Mazei-Robison
Understanding the brain circuitry that underlies reward is critical to improve treatment for many common health issues, including obesity, depression, and addiction. Here we focus on insights into the organization and function of reward circuitry and its synaptic and structural adaptations in response to cocaine exposure. While the importance of certain circuits, such as the mesocorticolimbic dopamine pathway, are well established in drug reward, recent studies using genetics-based tools have revealed functional changes throughout the reward circuitry that contribute to different facets of addiction, such as relapse and craving...
March 21, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28283562/effort-based-reinforcement-processing-and-functional-connectivity-underlying-amotivation-in-medicated-patients-with-depression-and-schizophrenia
#2
Ho Il Park, Boung Chul Lee, Jae-Jin Kim, Joong Il Kim, Min-Seung Koo
Amotivation is a common phenotype of major depressive disorder and schizophrenia which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted a functional MRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value as well as resting-state functional connectivities within the meso-striatal-prefrontal pathway...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28238767/evaluation-of-the-cart-peptide-expression-in-morphine-sensitization-in-male-rats
#3
Atefeh Bakhtazad, Nasim Vousooghi, Behzad Garmabi, Mohammad Reza Zarrindast
The importance of Cocaine- and amphetamine-regulated transcript (CART) peptide in reinforcing effects of addictive drugs specially alcohol and psychostimulants has been stablished. Involvement of CART peptide in rewarding effects of opioids in brain has recently been reported. Here we have studied the expression of CART mRNA and peptide in the reward pathway in morphine-induced sensitization phenomenon and also evaluated the peptide level fluctuations in CSF and plasma. Male Wistar rats received 7-day morphine injection (20mg/kg) and then after a 7-day washout period, a challenge dose of 10mg/kg morphine was administered and locomotor activity and oral stereotypical behaviors were recorded...
February 23, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28188587/circadian-rhythms-and-substance-abuse-chronobiological-considerations-for-the-treatment-of-addiction
#4
REVIEW
Ian C Webb
Reward-related learning, including that associated with drugs of abuse, is largely mediated by the dopaminergic mesolimbic pathway. Mesolimbic neurophysiology and motivated behavior, in turn, are modulated by the circadian timing system which generates ∼24-h rhythms in cellular activity. Both drug taking and seeking and mesolimbic dopaminergic neurotransmission can vary widely over the day. Moreover, circadian clock genes are expressed in ventral tegmental area dopaminergic cells and in mesolimbic target regions where they can directly modulate reward-related neurophysiology and behavior...
February 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/28185645/mu-opioid-receptors-in-gamma-aminobutyric-acidergic-forebrain-neurons-moderate-motivation-for-heroin-and-palatable-food
#5
Pauline Charbogne, Olivier Gardon, Elena Martín-García, Helen L Keyworth, Aya Matsui, Anna E Mechling, Thomas Bienert, Taufiq Nasseef, Anne Robé, Luc Moquin, Emmanuel Darcq, Sami Ben Hamida, Patricia Robledo, Audrey Matifas, Katia Befort, Claire Gavériaux-Ruff, Laura-Adela Harsan, Dominik von Elverfeldt, Jurgen Hennig, Alain Gratton, Ian Kitchen, Alexis Bailey, Veronica A Alvarez, Rafael Maldonado, Brigitte L Kieffer
BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28131769/suppression-of-inhibitory-g-protein-signaling-in-forebrain-pyramidal-neurons-triggers-plasticity-of-glutamatergic-neurotransmission-in-the-nucleus-accumbens-core
#6
Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Kevin Wickman
Cocaine and other drugs of abuse trigger long-lasting adaptations in excitatory and inhibitory neurotransmission in the mesocorticolimbic system, and this plasticity has been implicated in several key facets of drug addiction. For example, glutamatergic neurotransmission mediated by AMPA receptors (AMPAR) is strengthened in medium spiny neurons (MSNs) in the NAc core and shell during withdrawal following repeated in vivo cocaine administration. Repeated cocaine administration also suppresses inhibitory signaling mediated by G protein-gated inwardly rectifying K(+) (GIRK) channels in pyramidal neurons of the prelimbic cortex, an important source of glutamatergic input to the NAc core that has been implicated in cocaine-seeking and behavioral sensitization...
January 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28131626/alcohol-vapor-exposure-differentially-impacts-mesocorticolimbic-cytokine-expression-in-a-sex-region-and-duration-specific-manner
#7
Lydia N Baxter-Potter, Angela M Henricks, Anthony L Berger, Kennedy V Bieniasz, Janelle M Lugo, Ryan J McLaughlin
Alcohol exposure elicits the production of cytokines that regulate the host response to infection, immunity, inflammation, and trauma. Although increased production of pro-inflammatory cytokines has been linked to symptoms of alcoholism, few studies have evaluated whether cytokine expression changes across the development of alcohol dependence, or whether these changes are region and/or sex specific. In the present study, we subjected adult male and female rats to different regimens of alcohol vapor exposure (acute, subchronic, or chronic) and measured relative mRNA expression for tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) in reward-related brain regions...
January 25, 2017: Neuroscience
https://www.readbyqxmd.com/read/28123030/cocaine-promotes-coincidence-detection-and-lowers-induction-threshold-during-hebbian-associative-synaptic-potentiation-in-prefrontal-cortex
#8
Hongyu Ruan, Wei-Dong Yao
Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP)...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28123023/role-of-taar1-within-the-subregions-of-the-mesocorticolimbic-dopaminergic-system-in-cocaine-seeking-behavior
#9
Jian-Feng Liu, Justin N Siemian, Robert Seaman, Yanan Zhang, Jun-Xu Li
A novel G-protein coupled receptor, trace amine-associated receptor 1 (TAAR1), has been shown to be a promising target to prevent stimulant relapse. Our recent studies showed that systemic administration of TAAR1 agonists decreased abuse-related behaviors of cocaine. However, the role of TAAR1 in specific subregions of the reward system in drug addiction is unknown. Here, using a local pharmacological activation method, we assessed the role of TAAR1 within the subregions of the mesocorticolimbic system: that is, the VTA, the prelimbic cortex (PrL), and infralimbic cortex of medial prefrontal cortex, the core and shell of NAc, BLA, and CeA, on cue- and drug-induced cocaine-seeking in the rat cocaine reinstatement model...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28105985/impact-of-traumatic-brain-injury-on-dopaminergic-transmission
#10
Yuan-Hao Chen, Eagle Yi-Kung Huang, Tung-Tai Kuo, Jonathan Miller, Yung-Hsiao Chiang, Barry J Hoffer
Brain trauma is often associated with severe morbidity and is a major public health concern. Even when injury is mild and no obvious anatomic disruption is seen, many individuals suffer disabling neuropsychological impairments such as memory loss, mood dysfunction, substance abuse, and adjustment disorder. These changes may be related to subtle disruption of neural circuits as well as functional changes at the neurotransmitter level. In particular, there is considerable evidence that dopamine physiology in the nigrostriatal and mesocorticolimbic pathways might be impaired after TBI...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28042822/enduring-sexually-dimorphic-impact-of-in-utero-exposure-to-elevated-levels-of-glucocorticoids-on-midbrain-dopaminergic-populations
#11
REVIEW
Glenda E Gillies, Kanwar Virdee, Ilse Pienaar, Felwah Al-Zaid, Jeffrey W Dalley
Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life...
December 30, 2016: Brain Sciences
https://www.readbyqxmd.com/read/28032295/antagonism-of-muscarinic-acetylcholine-receptors-alters-synaptic-erk-phosphorylation-in-the-rat-forebrain
#12
Li-Min Mao, Henry H Wang, John Q Wang
Acetylcholine (ACh) is a key transmitter in the mesocorticolimbic circuit. By interacting with muscarinic ACh receptors (mAChR) enriched in the circuit, ACh actively regulates various neuronal and synaptic activities. The extracellular signal-regulated kinase (ERK) is one of members of the mitogen-activated protein kinase family and is subject to the regulation by dopamine receptors, although the regulation of ERKs by limbic mAChRs is poorly understood. In this study, we investigated the role of mAChRs in the regulation of ERK phosphorylation (activation) in the mesocorticolimbic system of adult rat brains in vivo...
December 28, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27993695/effects-of-orally-administered-augmentin-on-glutamate-transporter-1-cystine-glutamate-exchanger-expression-and-ethanol-intake-in-alcohol-preferring-rats
#13
Alqassem Y Hakami, Fahad S Alshehri, Yusuf S Althobaiti, Youssef Sari
Alcohol dependence is associated with deficits in glutamate uptake and impairment of glutamate homeostasis in different brain reward regions. Glutamate transporter subtype 1 (GLT-1), cystine-glutamate exchanger (xCT) and glutamate/aspartate transporter (GLAST) are one of the key players in regulating extracellular glutamate concentration in the brain. Parenteral treatment with ceftriaxone, β-lactam antibiotic, has been reported to attenuate ethanol consumption and reinstatement to cocaine-seeking behavior, in part, by restoring the expression of GLT-1 and xCT in mesocorticolimbic brain regions in rats...
March 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27986922/cocaine-promotes-coincidence-detection-and-lowers-induction-threshold-during-hebbian-associative-synaptic-potentiation-in-prefrontal-cortex
#14
Hongyu Ruan, Wei-Dong Yao
Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike timing-dependent LTP (t-LTP)...
December 16, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27980118/role-of-taar1-within-the-subregions-of-the-mesocorticolimbic-dopaminergic-system-in-cocaine-seeking-behavior
#15
Jian-Feng Liu, Justin N Siemian, Robert Seaman, Yanan Zhang, Jun-Xu Li
A novel G-protein coupled receptor, trace amine-associated receptor 1 (TAAR1), has been shown to be a promising target to prevent stimulant relapse. Our recent studies showed that systemic administration of TAAR1 agonists decreased abuse-related behaviors of cocaine. However, the role of TAAR1 in specific subregions of the reward system in drug addiction is unknown. Here, using a local pharmacological activation method, we assessed the role of TAAR1 within the subregions of the mesocorticolimbic system, i.e...
December 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27975173/acetyl-l-carnitine-via-upegulating-dopamine-d1-receptor-and-attenuating-microglial-activation-prevents-neuronal-loss-and-improves-memory-functions-in-parkinsonian-rats
#16
Sonu Singh, Akanksha Mishra, Neha Srivastava, Rakesh Shukla, Shubha Shukla
Parkinson's disease is accompanied by nonmotor symptoms including cognitive impairment, which precede the onset of motor symptoms in patients and are regulated by dopamine (DA) receptors and the mesocorticolimbic pathway. The relative contribution of DA receptors and astrocytic glutamate transporter (GLT-1) in cognitive functions is largely unexplored. Similarly, whether microglia-derived increased immune response affects cognitive functions and neuronal survival is not yet understood. We have investigated the effect of acetyl-L-carnitine (ALCAR) on cognitive functions and its possible underlying mechanism of action in 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats...
December 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27926436/to-work-or-not-to-work-neural-representation-of-cost-and-benefit-of-instrumental-action
#17
N B Kroemer, C Burrasch, L Hellrung
By definition, instrumental actions are performed in order to obtain certain goals. Nevertheless, the attainment of goals typically implies obstacles, and response vigor is known to reflect an integration of subjective benefit and cost. Whereas several brain regions have been associated with cost/benefit ratio decision-making, trial-by-trial fluctuations in motivation are not well understood. We review recent evidence supporting the motivational implications of signal fluctuations in the mesocorticolimbic system...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27914942/is-there-a-role-for-ghrelin-in-central-dopaminergic-systems-focus-on-nigrostriatal-and-mesocorticolimbic-pathways
#18
REVIEW
Alicia Stievenard, Mathieu Méquinion, Zane B Andrews, Alain Destée, Marie-Christine Chartier-Harlin, Odile Viltart, Christel C Vanbesien-Mailliot
The gastro-intestinal peptide ghrelin has been assigned many functions. These include appetite regulation, energy metabolism, glucose homeostasis, intestinal motility, anxiety, memory or neuroprotection. In the last decade, this pleiotropic peptide has been proposed as a therapeutic agent in gastroparesis for diabetes and in cachexia for cancer. Ghrelin and its receptor, which is expressed throughout the brain, play an important role in motivation and reward. Ghrelin finely modulates the mesencephalic dopaminergic signaling and is thus currently studied in pathological conditions including dopamine-related disorders...
February 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27894806/genetic-divergence-in-the-transcriptional-engram-of-chronic-alcohol-abuse-a-laser-capture-rna-seq-study-of-the-mouse-mesocorticolimbic-system
#19
Megan K Mulligan, Khyobeni Mozhui, Ashutosh K Pandey, Maren L Smith, Suzhen Gong, Jesse Ingels, Michael F Miles, Marcelo F Lopez, Lu Lu, Robert W Williams
Genetic factors that influence the transition from initial drinking to dependence remain enigmatic. Recent studies have leveraged chronic intermittent ethanol (CIE) paradigms to measure changes in brain gene expression in a single strain at 0, 8, 72 h, and even 7 days following CIE. We extend these findings using LCM RNA-seq to profile expression in 11 brain regions in two inbred strains - C57BL/6J (B6) and DBA/2J (D2) - 72 h following multiple cycles of ethanol self-administration and CIE. Linear models identified differential expression based on treatment, region, strain, or interactions with treatment...
February 2017: Alcohol
https://www.readbyqxmd.com/read/27890744/gene-expression-of-pro-opiomelanocortin-and-melanocortin-receptors-is-regulated-in-the-hypothalamus-and-mesocorticolimbic-system-following-nicotine-administration
#20
Damla E Tapinc, Rabia Ilgin, Egemen Kaya, Oguz Gozen, Muzeyyen Ugur, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure...
January 10, 2017: Neuroscience Letters
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