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https://www.readbyqxmd.com/read/28424564/new-developments-in-the-management-of-narcolepsy
#1
REVIEW
Vivien C Abad, Christian Guilleminault
Narcolepsy is a life-long, underrecognized sleep disorder that affects 0.02%-0.18% of the US and Western European populations. Genetic predisposition is suspected because of narcolepsy's strong association with HLA DQB1*06-02, and genome-wide association studies have identified polymorphisms in T-cell receptor loci. Narcolepsy pathophysiology is linked to loss of signaling by hypocretin-producing neurons; an autoimmune etiology possibly triggered by some environmental agent may precipitate hypocretin neuronal loss...
2017: Nature and Science of Sleep
https://www.readbyqxmd.com/read/28390877/effects-of-chronic-prenatal-mk-801-treatment-on-object-recognition-cognitive-flexibility-and-drug-induced-locomotor-activity-in-juvenile-and-adult-rat-offspring
#2
S Gallant, L Welch, P Martone, U Shalev
BACKGROUND: Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats...
April 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28373127/rp5063-an-atypical-antipsychotic-drug-with-a-unique-pharmacologic-profile-improves-declarative-memory-and-psychosis-in-mouse-models-of-schizophrenia
#3
Lakshmi Rajagopal, Sunoh Kwon, Mei Huang, Eric Michael, Laxminarayan Bhat, Marc Cantillon, Herbert Y Meltzer
Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4β2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied...
March 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28332334/-apaan-in-the-neck-a-reflection-on-some-novel-impurities-found-in-seized-materials-containing-amphetamine-in-ireland-during-routine-forensic-analysis
#4
John D Power, Pierce Kavanagh, Gavin McLaughlin, Michael Barry, Geraldine Dowling, Simon D Brandt
No abstract text is available yet for this article.
March 23, 2017: Drug Testing and Analysis
https://www.readbyqxmd.com/read/28322273/neuregulin-2-ablation-results-in-dopamine-dysregulation-and-severe-behavioral-phenotypes-relevant-to-psychiatric-disorders
#5
L Yan, A Shamir, M Skirzewski, E Leiva-Salcedo, O B Kwon, I Karavanova, D Paredes, O Malkesman, K R Bailey, D Vullhorst, J N Crawley, A Buonanno
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28303900/associations-between-behavioral-and-neural-correlates-of-inhibitory-control-and-amphetamine-reward-sensitivity
#6
Jessica Weafer, Stephanie M Gorka, Donald Hedeker, Mario Dzemidzic, David A Kareken, K Luan Phan, Harriet de Wit
Poor inhibitory control and sensitivity to drug reward are two significant risk factors for drug abuse. Although the two have been largely viewed as separate and independent risk factors, there is new evidence to suggest that they may be related at both the behavioral and neural level. This study examined associations between behavioral and neural correlates of inhibitory control and sensitivity to the subjective rewarding effects of amphetamine in humans. Healthy volunteers (n=63) first completed the stop signal task, a behavioral measure of inhibitory control...
March 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28294132/5-ht2c-agonists-modulate-schizophrenia-like-behaviors-in-mice
#7
Vladimir M Pogorelov, Ramona M Rodriguiz, Jianjun Cheng, Mei Huang, Claire M Schmerberg, Herbert Y Meltzer, Bryan L Roth, Alan P Kozikowski, William C Wetsel
All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side-effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests additional drug-targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss promoting capabilities...
March 15, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28285123/preclinical-predictors-that-the-orthosteric-mglu2-3-receptor-antagonist-ly3020371-will-not-engender-ketamine-associated-neurotoxic-motor-cognitive-subjective-or-abuse-liability-related-effects
#8
J M Witkin, J A Monn, J Li, B Johnson, D L McKinzie, X-S Wang, B A Heinz, R Li, P L Ornstein, S C Smith, C H Mitch, D O Calligaro, S Swanson, D Allen, K Phillips, G Gilmour
The novel mGlu2/3 receptor antagonist, LY3020371, has been shown to produce antidepressant-like effects comparable to that of the clinically-effective antidepressant ketamine. In the present study, we investigated whether LY3020371 would be predicted to be free of the side-effects and safety pharmacology issues associated with ketamine. In contrast to ketamine, LY3020371 produced small increases in locomotion and did not impair motor performance on an inverted screen. Ketamine, but not LY3020371, increased dopamine efflux in the nucleus accumbens of rats...
March 8, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28239338/differential-neural-responses-underlying-the-inhibition-of-the-startle-response-by-pre-pulses-or-gaps-in-mice
#9
Rocio Moreno-Paublete, Barbara Canlon, Christopher R Cederroth
Gap pre-pulse inhibition of the acoustic startle (GPIAS) is a behavioral paradigm used for inferring the presence of tinnitus in animal models as well as humans. In contrast to pre-pulse inhibition (PPI), the neural circuitry controlling GPIAS is poorly understood. To increase our knowledge on GPIAS, a comparative study with PPI was performed in mice combining these behavioral tests and c-Fos activity mapping in brain areas involved in the inhibition of the acoustic startle reflex (ASR). Both pre-pulses and gaps efficiently inhibited the ASR and abolished the induction of c-Fos in the pontine reticular nucleus...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28223211/sensitizing-exposure-to-amphetamine-increases-ampa-receptor-phosphorylation-without-increasing-cell-surface-expression-in-the-rat-nucleus-accumbens
#10
Qiang Wang, Dongdong Li, Nancy Bubula, Matthew R Campioni, Daniel S McGehee, Paul Vezina
Exposure to psychostimulants like cocaine or amphetamine leads to long-lasting sensitization of their behavioral and neurochemical effects. Here we characterized changes in AMPA receptor distribution and phosphorylation state in the rat nucleus accumbens (NAcc) weeks after amphetamine exposure to assess their potential contribution to sensitization by this drug. Using protein cross-linking, biochemical, subcellular fractionation, and slice electrophysiological approaches in the NAcc, we found that, unlike cocaine, previous exposure to amphetamine did not increase cell surface levels of either GluA1 or GluA2 AMPA receptor subunits, redistribution of these subunits to the synaptic or perisynaptic cellular membrane domains, protein-protein associations required to support the accumulation and retention of AMPA receptors in the PSD, or the peak amplitude of AMPA receptor mediated mEPSCs recorded in NAcc slices...
May 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28223210/a-novel-glp-1-gip-dual-receptor-agonist-protects-from-6-ohda-lesion-in-a-rat-model-of-parkinson-s-disease
#11
Jaishree Jalewa, Mohit Kumar Sharma, Simon Gengler, Christian Hölscher
The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors that have shown neuroprotective effects in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. GLP-1 analogues are currently on the market as treatments for type II diabetes. We previously showed that the novel dual agonist (DA-JC1) was effective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28167616/towards-trans-diagnostic-mechanisms-in-psychiatry-neurobehavioral-profile-of-rats-with-a-loss-of-function-point-mutation-in-the-dopamine-transporter-gene
#12
Valentina Vengeliene, Anton Bespalov, Martin Roßmanith, Sandra Horschitz, Stefan Berger, Ana L Relo, Hamid R Noori, Peggy Schneider, Thomas Enkel, Dusan Bartsch, Miriam Schneider, Berthold Behl, Anita C Hansson, Patrick Schloss, Rainer Spanagel
The Research Domain Criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here we used a new genetic rat model with a loss of function point mutation in the dopamine transporter (DAT) gene (Slc6a3_N157K) to systematically study the RDoC matrix (www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml). First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains - negative and positive valence systems, cognitive, social, and in arousal/regulatory systems...
February 6, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28163218/atypical-dopamine-efflux-caused-by-3-4-methylenedioxypyrovalerone-mdpv-via-the-human-dopamine-transporter
#13
Aparna Shekar, Jenny I Aguilar, Greta Galli, Nicholas V Cozzi, Simon D Brandt, Arnold E Ruoho, Michael H Baumann, Heinrich J G Matthies, Aurelio Galli
Synthetic cathinones are similar in chemical structure to amphetamines, and their behavioral effects are associated with enhanced dopaminergic signaling. The past ten years of research on the common constituent of bath salts, MDPV (the synthetic cathinone 3,4-methylenedioxypyrovalerone), has aided the understanding of how synthetic cathinones act at the dopamine (DA) transporter (DAT). Several groups have described the ability of MDPV to block the DAT with high-affinity. In this study, we demonstrate for the first time a new mode of action of MDPV, namely its ability to promote DAT-mediated DA efflux...
February 3, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28140405/the-impact-of-disrupted-in-schizophrenia-1-disc1-on-the-dopaminergic-system-a-systematic-review
#14
REVIEW
T Dahoun, S V Trossbach, N J Brandon, C Korth, O D Howes
Disrupted-in-Schizophrenia 1 (DISC1) is a gene known as a risk factor for mental illnesses possibly associated with dopamine impairments. DISC1 is a scaffold protein interacting with proteins involved in the dopamine system. Here we summarise the impact of DISC1 disruption on the dopamine system in animal models, considering its effects on presynaptic dopaminergic function (tyrosine hydroxylase levels, dopamine transporter levels, dopamine levels at baseline and after amphetamine administration) and postsynaptic dopaminergic function (dopamine D1 and D2 receptor levels, dopamine receptor-binding potential and locomotor activity after amphetamine administration)...
January 31, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#15
Jaakko J Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina L Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases, including drug addiction and Parkinson's disease. Because of its well established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been studied extensively in various disorders with disturbed dopamine homeostasis. However, the outcomes from preclinical and clinical studies vary, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
February 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28063587/indirect-chiral-separation-of-8-novel-amphetamine-derivatives-as-potential-new-psychoactive-compounds-by-gc-ms-and-hplc
#16
Jennifer A Weiß, Kian Kadkhodaei, Martin G Schmid
Amphetamine and its derivatives gained high popularity on the illegal drug market. In the last few years, a lot of new psychoactive compounds structurally related to amphetamine, such as 4-fluoroamphetamine and 4-fluoromethamphetamine swamped the drug market. They were designed to circumvent prohibition of amphetamine and N-methylamphetamine and are distributed via the Internet. Often, a halogen atom is introduced into the phenyl ring of amphetamine to turn the illegal amphetamine legal. Since amphetamines possess a chiral centre, two enantiomers are available, which might differ in activity...
January 2017: Science & Justice: Journal of the Forensic Science Society
https://www.readbyqxmd.com/read/28062254/the-effects-of-d-govadine-on-conditioned-place-preference-with-d-amphetamine-or-food-reward
#17
Maya O Nesbit, Carine Dias, Anthony G Phillips
Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28039543/sigma-receptors-and-alcohol-use-disorders
#18
Valentina Sabino, Pietro Cottone
Although extensive research has focused on understanding the neurobiological mechanisms underlying alcohol addiction, pharmacological treatments for alcohol use disorders are very limited and not always effective. This constraint has encouraged the search for novel pharmacological targets for alcoholism therapy. Sigma receptors were shown to mediate some of the properties of cocaine and amphetamine, which was attributed to the direct binding of psychostimulants to these receptors. More recently, the role of sigma receptors in the rewarding and reinforcing effects of alcohol was also proposed, and it was suggested that their hyperactivity may result in excessive alcohol drinking...
December 31, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28029499/development-of-an-enantioseparation-method-for-novel-psychoactive-drugs-by-hplc-using-a-lux-%C3%A2-cellulose-2-column-in-polar-organic-phase-mode
#19
Magdalena Taschwer, Jörg Grascher, Martin G Schmid
Since the last decade, the hype of the recreational use of novel psychoactive drugs is still on its top in entire Europe. Every year, new derivatives enter the drug market and enlarge the broad spectrum of misused drugs. Many of these compounds contain a stereogenic centre and therefore two enantiomers exist. It is obvious that the pharmacological potency of the isomers differ as it is already known from various pharmaceutical ingredients. Therefore, the development of analytical methods for the chiral separation of new psychoactive substances is of great medical and forensic interest...
October 20, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28003467/prefrontal-cortex-dysfunction-increases-susceptibility-to-schizophrenia-like-changes-induced-by-adolescent-stress-exposure
#20
Felipe V Gomes, Anthony A Grace
Stress during adolescence is a risk factor for schizophrenia, and medial prefrontal cortex (mPFC) dysfunction is proposed to interfere with stress control, increasing the susceptibility to stress. We evaluated the impact of different stressful events during adolescence (restraint stress [RS], footshock [FS], or the combination of FS and RS) on behaviors correlated with schizophrenia in rats as adults. At adulthood, animals were tested for anxiety responses (elevated plus-maze), cognitive function (novel-object recognition test) and dopamine (DA) system responsivity (locomotor response to amphetamine and DA neuron activity in the ventral tegmental area (VTA) using in vivo electrophysiology)...
May 1, 2017: Schizophrenia Bulletin
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