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Opioid-reward

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https://www.readbyqxmd.com/read/27707973/t394a-mutation-at-the-%C3%AE-opioid-receptor-blocks-opioid-tolerance-and-increases-vulnerability-to-heroin-self-administration-in-mice
#1
Xiao-Fei Wang, Elisabeth Barbier, Yi-Ting Chiu, Yi He, Jia Zhan, Guo-Hua Bi, Hai-Ying Zhang, Bo Feng, Lee-Yuan Liu-Chen, Jia Bei Wang, Zheng-Xiong Xi
: The etiology and pathophysiology underlying opioid tolerance and dependence are still unknown. Because mu opioid receptor (MOR) plays an essential role in opioid action, many vulnerability-related studies have focused on single nucleotide polymorphisms of MOR, particularly on A118G. In this study, we found that a single-point mutation at the MOR T394 phosphorylation site could be another important susceptive factor in the development of opioid tolerance and dependence in mice. T394A mutation, in which a threonine at 394 was replaced by an alanine, did not alter agonist binding to MOR and opioid analgesia, but resulted in loss of etorphine-induced MOR internalization in spinal dorsal horn neurons and opioid analgesic tolerance induced by either morphine or etorphine...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26468188/pain-and-poppies-the-good-the-bad-and-the-ugly-of-opioid-analgesics
#2
REVIEW
Tuan Trang, Ream Al-Hasani, Daniela Salvemini, Michael W Salter, Howard Gutstein, Catherine M Cahill
UNLABELLED: Treating pain is one of the most difficult challenges in medicine and a key facet of disease management. The isolation of morphine by Friedrich Sertürner in 1804 added an essential pharmacological tool in the treatment of pain and spawned the discovery of a new class of drugs known collectively as opioid analgesics. Revered for their potent pain-relieving effects, even Morpheus the god of dreams could not have dreamt that his opium tincture would be both a gift and a burden to humankind...
October 14, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26381438/probabilistic-reward-and-punishment-based-learning-in-opioid-addiction-experimental-and-computational-data
#3
Catherine E Myers, Jony Sheynin, Tarryn Balsdon, Andre Luzardo, Kevin D Beck, Lee Hogarth, Paul Haber, Ahmed A Moustafa
Addiction is the continuation of a habit in spite of negative consequences. A vast literature gives evidence that this poor decision-making behavior in individuals addicted to drugs also generalizes to laboratory decision making tasks, suggesting that the impairment in decision-making is not limited to decisions about taking drugs. In the current experiment, opioid-addicted individuals and matched controls with no history of illicit drug use were administered a probabilistic classification task that embeds both reward-based and punishment-based learning trials, and a computational model of decision making was applied to understand the mechanisms describing individuals' performance on the task...
January 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/26379484/effects-of-anabolic-androgens-on-brain-reward-function
#4
REVIEW
Emanuela Mhillaj, Maria G Morgese, Paolo Tucci, Maria Bove, Stefania Schiavone, Luigia Trabace
Androgens are mainly prescribed to treat several diseases caused by testosterone deficiency. However, athletes try to promote muscle growth by manipulating testosterone levels or assuming androgen anabolic steroids (AAS). These substances were originally synthesized to obtain anabolic effects greater than testosterone. Although AAS are rarely prescribed compared to testosterone, their off-label utilization is very wide. Furthermore, combinations of different steroids and doses generally higher than those used in therapy are common...
2015: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/26377910/phosphorylation-of-the-n-methyl-d-aspartate-receptor-is-increased-in-the-nucleus-accumbens-during-both-acute-and-extended-morphine-withdrawal
#5
Ethan M Anderson, Turi Reeves, Katherine Kapernaros, John K Neubert, Robert M Caudle
Opioid withdrawal causes a dysphoric state that can lead to complications in pain patients and can propagate use in drug abusers and addicts. Opioid withdrawal changes the activity of neurons in the nucleus accumbens, an area rich in both opioid-binding mu opioid receptors and glutamate-binding NMDA receptors. Because the accumbens is an area important for reward and aversion, plastic changes in this area during withdrawal could alter future behaviors in animals. We discovered an increase in phosphorylation of serine 897 in the NR1 subunit of the NMDA receptor (pNR1) during acute morphine withdrawal...
December 2015: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/26376284/dexmedetomidine-induces-conditioned-place-preference-in-rats-involvement-of-opioid-receptors
#6
Tuğçe Uskur, M Aydın Barlas, A Gökhan Akkan, Andleeb Shahzadi, Tayfun Uzbay
Dexmedetomidine (DEX) is an alpha-2 adrenergic agonist drug recently introduced to anesthesia practice. Certain agents used in anesthesia practice have been associated with abuse and addiction problems; however, few studies have investigated the role of DEX on addictive processes. Here, the effects and possible mechanisms of action of DEX on conditioned place preference (CPP), a model used for measuring the rewarding effects of drug abuse in rats, was investigated. The CPP apparatus was considered "biased" as the animals preferred the grid side to the mesh side...
January 1, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/26367865/glial-attenuation-with-ibudilast-in-the-treatment-of-medication-overuse-headache-a-double-blind-randomized-placebo-controlled-pilot-trial-of-efficacy-and-safety
#7
Jacinta L Johnson, Yuen H Kwok, Nicole M Sumracki, James E Swift, Mark R Hutchinson, Kirk Johnson, Desmond B Williams, Jonathon Tuke, Paul E Rolan
BACKGROUND: Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache...
October 2015: Headache
https://www.readbyqxmd.com/read/26364547/regulator-of-g-protein-signaling-7-regulates-reward-behavior-by-controlling-opioid-signaling-in-the-striatum
#8
Laurie P Sutton, Olga Ostrovskaya, Maria Dao, Keqiang Xie, Cesare Orlandi, Roy Smith, Sunmee Wee, Kirill A Martemyanov
BACKGROUND: Morphine mediates its euphoric and analgesic effects by acting on the μ-opioid receptor (MOR). MOR belongs to the family of G-protein coupled receptors whose signaling efficiency is controlled by the regulator of G-protein signaling (RGS) proteins. Our understanding of the molecular diversity of RGS proteins that control MOR signaling, their circuit specific actions, and underlying cellular mechanisms is very limited. METHODS: We used genetic approaches to ablate regulator of G-protein signaling 7 (RGS7) both globally and in specific neuronal populations...
August 1, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/26349634/differential-effects-of-oxycodone-hydrocodone-and-morphine-on-activation-levels-of-signaling-molecules
#9
Michael A Emery, M L Shawn Bates, Paul J Wellman, Shoshana Eitan
BACKGROUND: Opioids alter the responses of D2-like dopamine receptors (D2DRs), known to be involved in the pathology of addiction and other mental illnesses. Importantly, our recent results demonstrated that various opioids differentially modulate the behavioral responses of D2DRs. OBJECTIVE: To examine the effect of various opioids on striatal activation levels of Akt and ERK1/2, as well as the signaling responses of D2DRs following opioid exposure. METHODS: Mice were pre-treated with 20 mg/kg morphine, hydrocodone, oxycodone, or saline for 6 days...
September 9, 2015: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/26335648/distinct-subpopulations-of-nucleus-accumbens-dynorphin-neurons-drive-aversion-and-reward
#10
Ream Al-Hasani, Jordan G McCall, Gunchul Shin, Adrian M Gomez, Gavin P Schmitz, Julio M Bernardi, Chang-O Pyo, Sung Il Park, Catherine M Marcinkiewcz, Nicole A Crowley, Michael J Krashes, Bradford B Lowell, Thomas L Kash, John A Rogers, Michael R Bruchas
The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing...
September 2, 2015: Neuron
https://www.readbyqxmd.com/read/26325040/synthesis-and-characterization-of-a-dual-kappa-delta-opioid-receptor-agonist-analgesic-blocking-cocaine-reward-behavior
#11
András Váradi, Gina F Marrone, Shainnel O Eans, Michelle L Ganno, Joan J Subrath, Valerie Le Rouzic, Amanda Hunkele, Gavril W Pasternak, Jay P McLaughlin, Susruta Majumdar
3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0...
November 18, 2015: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/26305935/rgs9-2-controlled-adaptations-in-the-striatum-determine-the-onset-of-action-and-efficacy-of-antidepressants-in-neuropathic-pain-states
#12
Vasiliki Mitsi, Dimitra Terzi, Immanuel Purushothaman, Lefteris Manouras, Sevasti Gaspari, Rachael L Neve, Maria Stratinaki, Jian Feng, Li Shen, Venetia Zachariou
The striatal protein Regulator of G-protein signaling 9-2 (RGS9-2) plays a key modulatory role in opioid, monoamine, and other G-protein-coupled receptor responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood, reward, and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action...
September 8, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26269227/early-phase-in-the-development-of-cannabidiol-as-a-treatment-for-addiction-opioid-relapse-takes-initial-center-stage
#13
REVIEW
Yasmin L Hurd, Michelle Yoon, Alex F Manini, Stephanie Hernandez, Ruben Olmedo, Maria Ostman, Didier Jutras-Aswad
Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions...
October 2015: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/26260431/aberrant-mesolimbic-dopamine-opiate-interaction-in-obesity
#14
Lauri Tuominen, Jetro Tuulari, Henry Karlsson, Jussi Hirvonen, Semi Helin, Paulina Salminen, Riitta Parkkola, Jarmo Hietala, Pirjo Nuutila, Lauri Nummenmaa
Dopamine and opioid neurotransmitter systems share many functions such as regulation of reward and pleasure. μ-Opioid receptors (MOR) modulate the mesolimbic dopamine system in ventral tegmental area and striatum, key areas implicated in reward. We hypothesized that dopamine and opioid receptor availabilities correlate in vivo and that this correlation is altered in obesity, a disease with altered reward processing. Twenty lean females (mean BMI 22) and 25 non-binge eating morbidly obese females (mean BMI 41) underwent two positron emission tomography scans with [(11)C]carfentanil and [(11)C]raclopride to measure the MOR and dopamine D2 receptor (DRD2) availability, respectively...
November 15, 2015: NeuroImage
https://www.readbyqxmd.com/read/26258270/the-epidemiology-and-genetics-of-binge-eating-disorder-bed
#15
Caroline Davis
This narrative review provides an overview of the epidemiology of binge eating disorder (BED), highlighting the medical history of this disorder and its entry as an independent condition in the Feeding and Eating Disorders section of the recently published Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Estimates of prevalence are provided, as well as recognition that the female to male ratio is lower in BED than in other eating disorders. Evidence is also provided of the most common comorbidities of BED, including mood and anxiety disorders and a range of addiction disorders...
December 2015: CNS Spectrums
https://www.readbyqxmd.com/read/26256075/high-affinity-%C3%AE-3%C3%AE-4-nicotinic-acetylcholine-receptor-ligands-at-1001-and-at-1012-attenuate-cocaine-induced-conditioned-place-preference-and-behavioral-sensitization-in-mice
#16
Taline V Khroyan, Dennis Yasuda, Lawrence Toll, Willma E Polgar, Nurulain T Zaveri
Cholinergic signaling via the nicotinic acetylcholine receptors (nAChRs) in the mesolimbic circuitry is involved in the rewarding effects of abused drugs such as cocaine and opioids. In mouse studies, nonselective nAChR antagonist mecamylamine blocks cocaine-induced conditioned place preference (CPP) and behavioral sensitization. Among subtype-selective nAChR antagonists, the β2-selective antagonist dihydrobetaerythroidine and α7 antagonist methyllycaconitine (MLA), but not MLA alone prevent behavioral sensitization to cocaine...
October 15, 2015: Biochemical Pharmacology
https://www.readbyqxmd.com/read/26250442/possible-role-of-a-dysregulation-of-the-endogenous-opioid-system-in-antisocial-personality-disorder
#17
REVIEW
Borwin Bandelow, Dirk Wedekind
Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits...
November 2015: Human Psychopharmacology
https://www.readbyqxmd.com/read/26246443/the-imperial-college-cambridge-manchester-iccam-platform-study-an-experimental-medicine-platform-for-evaluating-new-drugs-for-relapse-prevention-in-addiction-part-a-study-description
#18
RANDOMIZED CONTROLLED TRIAL
Louise M Paterson, Remy S A Flechais, Anna Murphy, Laurence J Reed, Sanja Abbott, Venkataramana Boyapati, Rebecca Elliott, David Erritzoe, Karen D Ersche, Yetunde Faluyi, Luca Faravelli, Emilio Fernandez-Egea, Nicola J Kalk, Shankar S Kuchibatla, John McGonigle, Antonio Metastasio, Inge Mick, Liam Nestor, Csaba Orban, Filippo Passetti, Eugenii A Rabiner, Dana G Smith, John Suckling, Roger Tait, Eleanor M Taylor, Adam D Waldman, Trevor W Robbins, J F William Deakin, David J Nutt, Anne R Lingford-Hughes
Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: using functional magnetic resonance imaging (fMRI) techniques and selective pharmacological tools, it aims to explore the neuropharmacology of putative relapse pathways in cocaine, alcohol, opiate dependent, and healthy individuals to inform future drug development...
September 2015: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/26239494/relative-timing-between-kappa-opioid-receptor-activation-and-cocaine-determines-the-impact-on-reward-and-dopamine-release
#19
Elena H Chartoff, Shayla R Ebner, Angela Sparrow, David Potter, Phillip M Baker, Michael E Ragozzino, Mitchell F Roitman
Negative affective states can increase the rewarding value of drugs of abuse and promote drug taking. Chronic cocaine exposure increases levels of the neuropeptide dynorphin, an endogenous ligand at kappa opioid receptors (KOR) that suppresses dopamine release in the nucleus accumbens (NAc) and elicits negative affective states upon drug withdrawal. However, there is evidence that the effects of KOR activation on affective state are biphasic: immediate aversive effects are followed by delayed increases in reward...
March 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26229039/pituitary-adenylate-cyclase-activating-polypeptide-disrupts-motivation-social-interaction-and-attention-in-male-sprague-dawley-rats
#20
Rachel J Donahue, Archana Venkataraman, F Ivy Carroll, Edward G Meloni, William A Carlezon
BACKGROUND: Severe or prolonged stress can trigger psychiatric illnesses including mood and anxiety disorders. Recent work indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in regulating stress effects. In rodents, exogenous PACAP administration can produce persistent elevations in the acoustic startle response, which may reflect anxiety-like signs including hypervigilance. We investigated whether PACAP causes acute or persistent alterations in behaviors that reflect other core features of mood and anxiety disorders (motivation, social interaction, and attention)...
December 15, 2016: Biological Psychiatry
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