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Neuropsychopharmacology

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https://www.readbyqxmd.com/read/28091532/development-of-the-neuroimmune-modulator-ibudilast-for-the-treatment-of-alcoholism-a-randomized-placebo-controlled-human-laboratory-trial
#1
Lara A Ray, Spencer Bujarski, Steve Shoptaw, Daniel Jo Roche, Keith Heinzerling, Karen Miotto
Current directions in medication development for alcohol use disorder (AUD) emphasize the need to identify novel molecular targets and efficiently screen new compounds aimed at those targets. Ibudilast (IBUD) is a neuroimmune modulator that inhibits phosphodiesterases -4 and -10 and macrophage migration inhibitory factor and was recently found to reduce alcohol intake in rats by approximately 50%. To advance medications development for AUD, the present study consists of a randomized, crossover, double-blind, placebo-controlled laboratory study of IBUD in non-treatment seeking individuals with current (ie, past month) mild-to-severe AUD...
January 16, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28079061/progressive-decline-in-hippocampal-ca1-volume-in-individuals-at-ultra-high-risk-for-psychosis-who-do-not-remit-findings-from-the-longitudinal-youth-at-risk-study
#2
New Fei Ho, Daphne J Holt, Mike Cheung, Juan Eugenio Iglesias, Alex Goh, Mingyuan Wang, Joseph Kw Lim, Joshua de Souza, Joann S Poh, Yuen Mei See, Alison R Adcock, Stephen J Wood, Michael Wl Chee, Jimmy Lee, Juan Zhou
Most individuals identified as ultra high-risk for psychosis (UHR) do not develop frank psychosis. They continue to exhibit subthreshold symptoms, or go on to fully remit. Prior work has shown that the volume of CA1, a subfield of the hippocampus, is selectively reduced in the early stages of schizophrenia. Here, we aimed to determine whether patterns of volume change of CA1 are different in UHR individuals who do or do not achieve symptomatic remission. Structural MRI scans were acquired at baseline and at 1-2 follow-up time points (at 12-month intervals) from 147 UHR and healthy control subjects...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28079060/intranasal-lactoferrin-enhances-%C3%AE-secretase-dependent-amyloid-precursor-protein-processing-via-the-erk1-2-creb-and-hif-1%C3%AE-pathways-in-an-alzheimer-s-disease-mouse-model
#3
Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28079059/co-variation-of-peripheral-levels-of-mir-1202-and-brain-activity-and-connectivity-during-antidepressant-treatment
#4
Juan Pablo Lopez, Fabricio Pereira, Stéphane Richard-Devantoy, Marcelo Berlim, Eduardo Chachamovich, Laura M Fiori, Paola Niola, Gustavo Turecki, Fabrice Jollant
MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of Desvenlafaxine (50-100 mg die), twenty patients were scanned with 3T Magnetic Resonance Imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074831/rgs9-2-modulates-responses-to-oxycodone-in-pain-free-and-chronic-pain-states
#5
Sevasti Gaspari, Valeria Cogliani, Lefteris Manouras, Ethan M Anderson, Vasiliki Mitsi, Kleopatra Avrampou, Fiona B Carr, Venetia Zachariou
Regulator of G protein signalling 9-2 (RGS9-2) is a striatal enriched signal transduction modulator, known to play a critical role in the development of addiction-related behaviours following exposure to psychostimulants or opioids. RGS9-2 controls the function of several GPCRs, including dopamine and mu opioid (MOR) receptors. We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#6
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28059083/behavioral-determinants-of-cannabinoid-self-administration-in-old-world-monkeys
#7
William S John, Thomas J Martin, Michael A Nader
Reinforcing effects of Δ(9)-tetrahydrocannabinol (THC), the primary active ingredient in marijuana, as assessed with self-administration (SA), has only been established in New World primates (squirrel monkeys). The objective of this study was to investigate some experimental factors that may enhance intravenous SA of THC and the cannabinoid receptor (CBR) agonist CP 55 940 in Old World monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. In one experiment, male rhesus monkeys (N=9) were trained to respond under a fixed-ratio 10 schedule of food presentation...
January 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28051103/maladaptive-sex-behavior-following-concurrent-methamphetamine-and-sexual-experience-in-male-rats-is-associated-with-altered-neural-activity-in-frontal-cortex
#8
Lindsey B Kuiper, Karla S Frohmader, Lique M Coolen
The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated that methamphetamine (Meth), when administered concurrently with sexual behavior show impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior and the effects of concurrent Meth and sexual behavior on neural activity in these pathways, using ERK phosphorylation (pERK) as neural activity marker...
January 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28042872/infralimbic-glun2a-containing-nmda-receptors-modulate-reconsolidation-of-cocaine-self-administration-memory
#9
Madalyn Hafenbreidel, Carolynn Rafa Todd, Devin Mueller
Addiction is characterized by high relapse susceptibility, and relapse can be triggered by drug-associated cues. Cue presentation induces retrieval of the drug-cue memory, which becomes labile and must be reconsolidated into long-term storage. Repeated unpaired cue presentation, however, induces extinction. Cue-reactivity can be reduced by blocking reconsolidation or facilitating extinction, which are mediated by NMDA receptors (NMDArs). However, the role of NMDArs in either process following self-administration is unclear...
January 2, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28042871/acute-d3-antagonist-gsk598809-selectively-enhances-neural-response-during-monetary-reward-anticipation-in-drug-and-alcohol-dependence
#10
Anna Murphy, Liam J Nestor, John McGonigle, Louise Paterson, Venkataramana Boyapati, Karen D Ersche, Remy Flechais, Shankar Kuchibatla, Antonio Metastasio, Csaba Orban, Filippo Passetti, Laurence Reed, Dana Smith, John Suckling, Eleanor Taylor, Trevor W Robbins, Anne Lingford-Hughes, David J Nutt, John Fw Deakin, Rebecca Elliott
: Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the go/no-go task (GNGT)...
January 2, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28042870/obesity-induced-structural-and-neuronal-plasticity-in-the-lateral-orbitofrontal-cortex
#11
Jennifer L Thompson, Michael Drysdale, Corey Baimel, Manpreet Kaur, Taigan MacGowan, Kimberley A Pitman, Stephanie L Borgland
The orbitofrontal cortex (OFC) integrates sensory information with the current value of foods and updates actions based on this information. Obese humans and rats fed a cafeteria diet have impaired devaluation of food rewards, implicating a potential obesity-induced dysfunction of the OFC. We hypothesized that obesity alters OFC pyramidal neuronal structure and function and reduces conditioned suppression of feeding. Rats were given restricted (1 h/day), extended (23 h/day) or no (chow only) access to a cafeteria diet and tested for a conditioned suppression of feeding...
January 2, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28041692/neurofeedback-one-of-today-s-techniques-in-psychiatry
#12
M Arns, J-M Batail, S Bioulac, M Congedo, C Daudet, D Drapier, T Fovet, R Jardri, M Le-Van-Quyen, F Lotte, D Mehler, J-A Micoulaud-Franchi, D Purper-Ouakil, F Vialatte
OBJECTIVES: Neurofeedback is a technique that aims to teach a subject to regulate a brain parameter measured by a technical interface to modulate his/her related brain and cognitive activities. However, the use of neurofeedback as a therapeutic tool for psychiatric disorders remains controversial. The aim of this review is to summarize and to comment the level of evidence of electroencephalogram (EEG) neurofeedback and real-time functional magnetic resonance imaging (fMRI) neurofeedback for therapeutic application in psychiatry...
December 29, 2016: L'Encéphale
https://www.readbyqxmd.com/read/28025975/incubation-of-methamphetamine-but-not-heroin-craving-after-voluntary-abstinence-in-male-and-female-rats
#13
Marco Venniro, Michelle Zhang, Yavin Shaham, Daniele Caprioli
We recently introduced an animal model of incubation of methamphetamine craving after choice-based voluntary abstinence in male rats. Here, we studied the generality of this phenomenon to (1) female rats, and (2) male and female rats with a history of heroin self-administration. We first trained rats to self-administer palatable food pellets for 6 days (6 h/day) for either methamphetamine (0.1 mg/kg/infusion) or heroin (0.1 mg/kg/infusion) for 12 days (6 h/day). We then assessed relapse to drug seeking in extinction tests after 1 and 21 abstinence days...
December 27, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28025974/social-status-in-monkeys-effects-of-social-confrontation-on-brain-function-and-cocaine-self-administration
#14
R W Gould, P W Czoty, L J Porrino, M A Nader
Understanding individual differences in response to social stress and environmental enrichment on brain function and drug abuse may help explain the variability in response to behavioral and pharmacological treatments for drug addiction. In monkeys, social status influences the reinforcing effects of cocaine and the effects of some drugs on cocaine self-administration. In this study, we used male cynomolgus macaques (n=15) living in established social groups to examine the effects of social confrontation on the reinforcing effects of cocaine using a food-drug choice procedure...
December 27, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28025973/lateral-habenula-involvement-in-impulsive-cocaine-seeking
#15
Agustin Zapata, Eun-Kyung Hwang, Carl R Lupica
The lateral habenula (LHb) is a brain structure receiving inputs from limbic forebrain areas and innervating major midbrain monoaminergic nuclei. Evidence indicates LHb involvement in sleep control, reward-based decision making, avoidance of punishment, and responses to stress. Additional work has established that the LHb mediates negative feedback in response to aversive events. As a hallmark of drug addiction is the inability to limit drug use despite negative consequences, we hypothesize that LHb dysfunction may have a role in the lack of control over drug seeking...
December 27, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27995932/intranasal-oxytocin-and-vasopressin-modulate-divergent-brainwide-functional-substrates
#16
Alberto Galbusera, Alessia De Felice, Girardi Stefano, Giacomo Bassetto, Marta Maschietto, Katsuhiko Nishimori, Bice Chini, Francesco Papaleo, Stefano Vassanelli, Alessandro Gozzi
The neuropeptides oxytocin (OXT) and vasopressin (AVP) have been identified as modulators of emotional social behaviours, and associated with neuropsychiatric disorders characterized by social dysfunction. Experimental and therapeutic use of OXT and AVP via the intranasal route is the subject of extensive clinical research. However, the large-scale functional substrates directly engaged by these peptides and their functional dynamics remain elusive. By using cerebral blood volume (CBV) weighted fMRI in the mouse we show that intranasal administration of OXT rapidly elicits the transient activation of cortical regions, and a sustained activation of hippocampal and forebrain areas characterised by high oxytocin receptor density...
December 20, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27986975/roles-of-hippocampal-somatostatin-receptor-subtypes-in-stress-response-and-emotionality
#17
Thomas D Prévôt, François Gastambide, Cécile Viollet, Nadia Henkousl, Guillaume Martel, Jacques Epelbaum, Daniel Béracochéa, Jean-Louis Guillou
Altered brain somatostatin functions recently appeared as key elements for the pathogenesis of stress related neuropsychiatric disorders. The hippocampus exerts an inhibitory feedback on stress but the mechanisms involved remain unclear. We investigated herein the role of hippocampal somatostatin receptor subtypes in both stress response and behavioral emotionality using C57BL/6, wild type and sst2 or sst4 knockout mice. Inhibitory effects of hippocampal infusions of somatostatin agonists on stress-induced hypothalamo-pituitary-adrenal axis (HPA) activity were tested by monitoring peripheral blood and local hippocampus corticosterone levels, the latter by using microdialysis...
December 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27986974/effects-of-a-serotonin-2c-agonist-and-a-2a-antagonist-on-actigraphy-based-sleep-parameters-disrupted-by-methamphetamine-self-administration-in-rhesus-monkeys
#18
Maylen Perez Diaz, Monica L Andersen, Kenner C Rice, Leonard L Howell
Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT2C receptor agonist, WAY163909, and a 5-HT2A receptor antagonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in nonhuman primates...
December 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27986973/dysregulation-of-specialized-delay-interference-dependent-working-memory-following-loss-of-dysbindin-1a-in-schizophrenia-related-phenotypes
#19
Emilie I Petit, Zuzanna Michalak, Rachel Cox, C M P O'Tuathaigh, Niamh Clarke, Orna Tighe, Konrad Talbot, Derek Blake, Josephine Joel, Alexander Shaw, Steven A Sheardown, Alastair D Morrison, Stephen Wilson, Ellen M Shapland, David C Henshall, James N Kew, Brian P Kirby, John L Waddington
Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B and C) remain unknown, we generated a novel mutant mouse, dys-1A(-/-), with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment...
December 16, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27976681/amphetamine-and-methamphetamine-increase-nmdar-glun2b-synaptic-currents-in-midbrain-dopamine-neurons
#20
Minghua Li, Suzanne M Underhill, Cheryl Reed, Tamara J Phillips, Susan G Amara, Susan L Ingram
The psychostimulants amphetamine (AMPH) and methamphetamine (MA) are widely abused illicit drugs. Here we show that both psychostimulants acutely increase NMDA receptor (NMDAR)-mediated synaptic currents and decrease AMPAR/NMDAR ratios in midbrain dopamine neurons. The potentiation depends on the transport of AMPH into the cell by the dopamine transporter (DAT). NMDAR-GluN2B receptor inhibitors, ifenprodil, RO 25-6981 and RO 04-5595 inhibit the potentiation without affecting basal evoked NMDA currents, indicating that NMDAR-GluN2B receptors are activated by AMPH...
December 15, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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