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D L McCue, J M Kasper, J D Hommel
BACKGROUND: Motivation for high-fat food is thought to contribute to excess caloric intake in obese individuals. A novel regulator of motivation for food may be Neuromedin U (NMU), a highly-conserved neuropeptide which influences food intake. Although these effects of NMU have primarily been attributed to signaling in the paraventricular nucleus of the hypothalamus (PVN), NMU has also been found in other brain regions involved in both feeding behavior and motivation. We investigate the effects of NMU on motivation for food and food intake, and identify the brain regions mediating these effects...
October 17, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Morgane Milienne-Petiot, James P Kesby, Mary Graves, Jordy van Enkhuizen, Svetlana Semenova, Arpi Minassian, Athina Markou, Mark A Geyer, Jared W Young
BACKGROUND: Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses...
October 9, 2016: Neuropharmacology
Shi-Xun Ma, Seung-Hwan Kwon, Jee-Yeon Seo, Ji-Young Hwang, Sa-Ik Hong, Hyoung-Chun Kim, Seok-Yong Lee, Choon-Gon Jang
Transient receptor potential vanilloid type 1 (TRPV1), the archetypal member of the vanilloid TRP family, was initially identified as the receptor for capsaicin, the pungent ingredient in hot chili peppers. We previously demonstrated that TRPV1 in the dorsal striatum significantly contributes to morphine reward by using the conditioned place preference paradigm in mice; however, it is unknown whether TRPV1 has the same effect in other reward models. In this study, we investigated the role of TRPV1 in morphine reward by using a self-administration paradigm in rats...
October 11, 2016: Addiction Biology
Jeffrey S Stein, A George Wilson, Mikhail N Koffarnus, Michael C Judd, Warren K Bickel
RATIONALE: Behavioral economic measures of demand provide estimates of tobacco product abuse liability and may predict effects of policy-related price regulation on consumption of existing and emerging tobacco products. OBJECTIVE: In the present study, we examined demand for snus, a smokeless tobacco product, in comparison to both cigarettes and medicinal nicotine. We used both a naturalistic method in which participants purchased these products for use outside the laboratory, as well as laboratory-based self-administration procedures...
October 11, 2016: Psychopharmacology
Fair M Vassoler, David J Oliver, Cristina Wyse, Ashley Blau, Michael Shtutman, Jill R Turner, Elizabeth M Byrnes
The United States is in the midst of an opiate epidemic, with abuse of prescription and illegal opioids increasing steadily over the past decade. While it is clear that there is a genetic component to opioid addiction, there is a significant portion of heritability that cannot be explained by genetics alone. The current study was designed to test the hypothesis that maternal exposure to opioids prior to pregnancy alters abuse liability in subsequent generations. Female adolescent Sprague Dawley rats were administered morphine at increasing doses (5-25 mg/kg, s...
October 8, 2016: Neuropharmacology
Emma Yhnell, Stephen B Dunnett, Simon P Brooks
Huntington's disease (HD) is characterised by motor symptoms which are often preceded by cognitive and behavioural changes, that can significantly contribute to disease burden for people living with HD. Numerous knock-in mouse models of HD are currently available for scientific research. However, before their use, they must be behaviourally characterised to determine their suitability in recapitulating the symptoms of the human condition. Thus, we sought to longitudinally characterise the nature, severity and time course of cognitive and behavioural changes observed in HdhQ111 heterozygous knock-in mice...
2016: PloS One
Teri M Furlong, Jhodie R Duncan, Laura H Corbit, Caroline D Rae, Benjamin D Rowlands, Anthony D Maher, Fatima A Nasrallah, Carol J Milligan, Steven Petrou, Andrew J Lawrence, Bernard W Balleine
Toluene is a commonly abused inhalant that is easily accessible to adolescents. Despite the increasing incidence of use, our understanding of its long-term impact remains limited. Here we used a range of techniques to examine the acute and chronic effects of toluene exposure on glutameteric and GABAergic function, and on indices of psychological function in adult rats after adolescent exposure. Metabolomics conducted on cortical tissue established that acute exposure to toluene produces alterations in cellular metabolism indicative of a glutamatergic and GABAergic profile...
October 1, 2016: Journal of Neurochemistry
Scott T Barrett, Trevor N Geary, Amy N Steiner, Rick A Bevins
RATIONALE: Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. OBJECTIVES: The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach...
October 1, 2016: Psychopharmacology
Lisa R Gerak, Gregory T Collins, Charles P France
Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin2C (5-HT2C) receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion)...
September 20, 2016: Journal of Pharmacology and Experimental Therapeutics
Margaret C Wardle, Jessica N Vincent, Robert Suchting, Charles E Green, Scott D Lane, Joy M Schmitz
This study explored anhedonia (lack of interest or pleasure in non-drug rewards) as a potentially modifiable individual difference associated with the effectiveness of Contingency Management (CM). It also tested the hypothesis that a dopaminergic drug, levodopa (L-DOPA), would improve the effectiveness of CM, particularly in individuals high in anhedonia. The study was a single-site, randomized, double-blind, parallel group, 12-week trial comparing L-DOPA with placebo, with both medication groups receiving voucher-based CM targeting cocaine-negative urines...
September 9, 2016: Journal of Substance Abuse Treatment
P Elliott Miller, Di Zhao, Alexis C Frazier-Wood, Erin D Michos, Michelle Averill, Veit Sandfort, Gregory L Burke, Joseph F Polak, Joao A C Lima, Wendy S Post, Roger S Blumenthal, Eliseo Guallar, Seth S Martin
BACKGROUND: Coffee and tea are two of the most commonly consumed beverages in the world. The association of coffee and tea intake with coronary artery calcium and major adverse cardiovascular events remains uncertain. METHODS: We examined 6,508 ethnically-diverse participants with available coffee and tea data from the Multi-Ethnic Study of Atherosclerosis. Intake for each was classified as never, occasional (<1 cup/day), and regular (≥1 cup/day). A coronary artery calcium progression ratio was derived from mixed effect regression models using loge(calcium score+1) as the outcome with coefficients exponentiated to reflect coronary artery calcium progression ratio vs...
September 15, 2016: American Journal of Medicine
Ashraf Mahmud, Stephanie Gallant, Firas Sedki, Tracey D'Cunha, Uri Shalev
Cannabidiol is a non-psychoactive compound that is the second most abundant component of cannabis. It has been shown to have a potential therapeutic value for a wide range of disorders, including anxiety, psychosis, and depression. Recently, it was suggested that cannabidiol might be a potential treatment for heroin craving and relapse. Here we investigated the effects of an acute treatment with cannabidiol on cocaine self-administration and cue-induced cocaine seeking in rats. Rats were trained to press a lever to self-administer cocaine (0...
September 13, 2016: Journal of Psychopharmacology
Alyssa N Wilson, Olivia H Gratz
A handful of studies have examined the utility of progressive ratio schedules (PRs) of reinforcement in treatment development and treatment efficacy. The current case study explored the utility of PRs as an assessment tool to inform a differential reinforcement treatment package. A PRs assessment was used to identify the breaking point of a functional communicative response before and after treatment. The breaking point was used as the initial reinforcement schedule during treatment. Following treatment, the communicative response increased during a posttest PRs assessment, suggesting the efficacy of the treatment package...
September 2016: Behavior Analysis in Practice
Jessica Millar, David K Bilkey, Ryan D Ward
Epidemiological studies have provided convincing evidence for a role of maternal immune activation in the pathogenesis of neurodevelopmental disorders such as autism and schizophrenia. In recent years, several research groups have capitalised on this discovery and developed animal models such as the maternal immune activation (MIA) model that emulates many phenotypes characteristic of disorders such as schizophrenia. In the present series of experiments we used the MIA model to examine motivation, a core component of the negative symptomatology in schizophrenia...
September 1, 2016: Brain, Behavior, and Immunity
E Galaj, W Harding, R Ranaldi
RATIONALE: Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking. PURPOSE AND METHODS: Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats. RESULTS: The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking...
August 31, 2016: Psychopharmacology
Urszula Skupio, Magdalena Sikora, Michal Korostynski, Agnieszka Wawrzczak-Bargiela, Marcin Piechota, Joanna Ficek, Ryszard Przewlocki
Chronic exposure to opioids induces adaptations in brain function that lead to the formation of the behavioral and physiological symptoms of drug dependence and addiction. Animal models commonly used to test these symptoms typically last less than two weeks, which is presumably too short to observe the alterations in the brain that accompany drug addiction. Here, we analyzed the phenotypic and molecular effects of nearly lifelong morphine or saccharin intake in C57BL/6J mice. We used multiple paradigms to evaluate the symptoms of compulsive drug intake: a progressive ratio schedule, intermittent access and a schedule involving a risk of punishment were programmed into an automated IntelliCage system...
August 31, 2016: Addiction Biology
Huiping Ding, Paul W Czoty, Norikazu Kiguchi, Gerta Cami-Kobeci, Devki D Sukhtankar, Michael A Nader, Stephen M Husbands, Mei-Chuan Ko
Despite the critical need, no previous research has substantiated safe opioid analgesics without abuse liability in primates. Recent advances in medicinal chemistry have led to the development of ligands with mixed mu opioid peptide (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor agonist activity to achieve this objective. BU08028 is a novel orvinol analog that displays a similar binding profile to buprenorphine with improved affinity and efficacy at NOP receptors. The aim of this preclinical study was to establish the functional profile of BU08028 in monkeys using clinically used MOP receptor agonists for side-by-side comparisons in various well-honed behavioral and physiological assays...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jirawoot Srisontiyakul, Hanna E Kastman, Elena V Krstew, Piyarat Govitrapong, Andrew J Lawrence
Cigarettes and alcohol are the most abused substances in the world and are commonly co-abused. Nicotine primarily acts in the brain on nicotinic acetylcholine receptors (nAChR), which are also a target for alcohol. The alpha6 subunit of nAChR is expressed almost exclusively in the brain reward system and may modulate the rewarding properties of alcohol and nicotine. Recently, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI) was synthesized as a selective, brain penetrant α6 subunit antagonist that reduces nicotine self-administration...
August 29, 2016: Neurochemical Research
Brooke E Schmeichel, Melissa A Herman, Marisa Roberto, George F Koob
BACKGROUND: Cocaine addiction is characterized by patterns of compulsive drug-taking, including preoccupation with obtaining cocaine and loss of control over drug intake. The lateral hypothalamic hypocretin/orexin (HCRT) system has been implicated in drug-taking and the reinstatement of drug-seeking. Evidence suggests that HCRT may drive drug-seeking through activation of specific brain regions implicated in stress system dysfunction, including the central amygdala (CeA). The role of HCRT in the persistence of compulsive-like cocaine-taking has yet to be fully elucidated...
June 16, 2016: Biological Psychiatry
Marsida Kallupi, Giulia Scuppa, Giordano de Guglielmo, Girolamo Calò, Friedbert Weiss, Michael A Statnick, Linda M Rorick-Kehn, Roberto Ciccocioppo
The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the nociceptin/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (-/-) rats to study the motivation for cocaine, heroin and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0...
August 26, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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