Jason M Uslaner
Affiliation: Merck Research Laboratories
- Subthalamic nucleus lesions increase impulsive action and decrease impulsive choice - mediation by enhanced incentive motivation?Jason M Uslaner
Biopsychology and Neuroscience Programs, Department of Psychology, University of Michigan, East Hall, 525 E University Street, Ann Arbor, MI 48019 1109, USA
Eur J Neurosci 24:2345-54. 2006..These findings suggest that the STN may serve as a novel target for the treatment of psychological disorders characterized by deficits in behavioral control, such as drug addiction and attention deficit hyperactivity disorder...
- T-type calcium channel antagonism produces antipsychotic-like effects and reduces stimulant-induced glutamate release in the nucleus accumbens of ratsJason M Uslaner
Department of Neuroscience, Merck and Co, Inc, WP46 300, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486, USA
Neuropharmacology 62:1413-21. 2012..Basal, amphetamine- and MK-801-induced dopamine efflux was altered. These findings suggest that T-type calcium channel antagonism could represent a novel mechanism for treating schizophrenia...
- The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy thresholdAnthony L Gotter
Department of Neuroscience, Merck Research Laboratories, West Point, PA, USA
BMC Neurosci 14:90. 2013..These features of an ideal compound are not only dependent upon pharmacokinetics, receptor binding kinetics, potency and pharmacodynamic activity, but also upon a compound's mechanism of action...
- Selective orexin 2 receptor antagonism blocks cue-induced reinstatement, but not nicotine self-administration or nicotine-induced reinstatementJason M Uslaner
Departments of Pharmacology, Merck and Co, Inc, West Point, PA 19486, USA Electronic address
Behav Brain Res 269:61-5. 2014..These findings indicate that orexin 2 receptor antagonism might have utility for attenuating relapse, particularly for patients sensitive to environmental stimuli associated with drug taking...
- Orexin receptor antagonists differ from standard sleep drugs by promoting sleep at doses that do not disrupt cognitionJason M Uslaner
Merck and Co Inc, WP46 100, 770 Sumneytown Pike, P O Box 4, West Point, PA 19486, USA
Sci Transl Med 5:179ra44. 2013..These findings suggest that DORAs might provide an effective treatment for insomnia with a greater therapeutic margin for sleep versus cognitive disturbances compared to the GABAA-positive allosteric modulators currently in use...
- The muscarinic M1 receptor positive allosteric modulator PQCA improves cognitive measures in rat, cynomolgus macaque, and rhesus macaqueJason M Uslaner
Merck Research Laboratories, Merck and Co, Inc, West Point, PA 19486, USA
Psychopharmacology (Berl) 225:21-30. 2013....
- The influence of subthalamic nucleus lesions on sign-tracking to stimuli paired with food and drug rewards: facilitation of incentive salience attribution?Jason M Uslaner
Department of Schizophrenia, Merck Research Laboratories, West Point, PA 19486, USA
Neuropsychopharmacology 33:2352-61. 2008..Activity in this neural system may help mitigate the development of compulsive behavioral disorders, such as addiction, which are characterized by pathological control over behavior by reward-associated cues...
- Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampusJason M Uslaner
Department of Schizophrenia Research, Merck and Co, Inc, West Point, PA 19486, USA
Neuropharmacology 57:531-8. 2009..These findings may have important implications for the development of mGluR5 PAMs to treat schizophrenia...
- Combined administration of an mGlu2/3 receptor agonist and a 5-HT 2A receptor antagonist markedly attenuate the psychomotor-activating and neurochemical effects of psychostimulantsJason M Uslaner
Department of Schizophrenia Research, Merck and Co, Inc, 770 Sumneytown Pike, West Point, PA 19486, USA
Psychopharmacology (Berl) 206:641-51. 2009..However, at the single, potentially suboptimal, dose that was tested, LY2140023 trended towards being inferior to olanzapine on several indices of efficacy within the Positive and Negative Syndrome Scale...
- Inhibition of glycine transporter 1 attenuates nicotine- but not food-induced cue-potentiated reinstatement for a response previously paired with sucroseJason M Uslaner
Department of Schizophrenia Research, Merck and Co, Inc, Ann Arbor, MI 48019 1109, USA
Behav Brain Res 207:37-43. 2010..Here we examined the effects of a glycine transporter (GlyT1) inhibitor, which elevates glycine and hence NMDA signaling, on the behavioral effects of nicotine...
- T-type calcium channel antagonism decreases motivation for nicotine and blocks nicotine- and cue-induced reinstatement for a response previously reinforced with nicotineJason M Uslaner
Department of Neuroscience, Merck and Co, Inc, West Point, Pennsylvania 19486, USA
Biol Psychiatry 68:712-8. 2010..Recent evidence suggests an involvement of T-type calcium channels in the effects of drugs of abuse...
- The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkeySean M Smith
Neuroscience, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA
Neuropharmacology 64:215-23. 2013..This article is part of a Special Issue entitled 'Cognitive Enhancers'...
- The nicotinic α7 receptor agonist GTS-21 improves cognitive performance in ketamine impaired rhesus monkeysChristopher E Cannon
Merck Research Laboratories 44E 200, 770 Sumneytown Pike, West Point, PA 19486, USA
Neuropharmacology 64:191-6. 2013..This article is part of a Special Issue entitled 'Cognitive Enhancers'...
- Orexin receptor antagonism prevents transcriptional and behavioral plasticity resulting from stimulant exposureChristopher J Winrow
Depression and Circadian Disorders Department, Merck Research Laboratories, West Point, PA, USA
Neuropharmacology 58:185-94. 2010....
- MK-801 produces a deficit in sucrose preference that is reversed by clozapine, D-serine, and the metabotropic glutamate 5 receptor positive allosteric modulator CDPPB: relevance to negative symptoms associated with schizophrenia?Joshua D Vardigan
Merck and Co, Inc, West Point, PA 19486, USA
Pharmacol Biochem Behav 95:223-9. 2010..These data suggest that this model may be useful for identifying novel agents that improve negative symptoms, and that compounds which enhance NMDA receptor function, such as mGlu5 receptor PAMs, may have clinical utility in this regard...
- Differential effects of the mGluR5 positive allosteric modulator CDPPB in the cortex and striatum following repeated administrationSophie Parmentier-Batteur
Department of Psychiatry, Merck and Co, Inc, West Point, PA 19486, USA
Neuropharmacology 62:1453-60. 2012....
- Quantitative electroencephalography within sleep/wake states differentiates GABAA modulators eszopiclone and zolpidem from dual orexin receptor antagonists in ratsSteven V Fox
Department of Neuroscience, Merck Research Laboratories, Merck Corporation, West Point, PA, USA
Neuropsychopharmacology 38:2401-8. 2013..These results suggest that DORA-22 differs from eszopiclone and zolpidem whereby DORA-22 promotes somnolence without altering the neuronal network EEG activity observed during normal sleep. ..
- The behavioral and neurochemical effects of a novel D-amino acid oxidase inhibitor compound 8 [4H-thieno [3,2-b]pyrrole-5-carboxylic acid] and D-serineSean M Smith
Department of Schizophrenia Research, Merck and Co, Inc, WP46 100, 770 Sumneytown Pike, P O Box 4, West Point, PA 19486, USA
J Pharmacol Exp Ther 328:921-30. 2009....
- Inhibition of Orexin Signaling Promotes Sleep Yet Preserves Salient Arousability in MonkeysPamela L Tannenbaum
Department of Pharmacology, Merck Research Laboratories, Merck and Co, Inc, West Point, PA
Sleep 39:603-12. 2016....
- Cocaine-induced psychomotor activity is associated with its ability to induce c-fos mRNA expression in the subthalamic nucleus: effects of dose and repeated treatmentJason M Uslaner
Biopsychology Program, Department of Psychology, The University of Michigan, East Hall, 525 E University St, Ann Arbor, MI 48019 1109, USA
Eur J Neurosci 17:2180-6. 2003..These findings may have implications concerning the neurobiological mechanisms underlying the behavioural effects of psychostimulant drugs...
- Optimization of Novel Aza-benzimidazolone mGluR2 PAMs with Respect to LLE and PK Properties and Mitigation of CYP TDIJOSEPH E PERO
Departments of Medicinal Chemistry, In Vitro Sciences, Psychiatry Research, Central Pharmacology, Drug Metabolism, Process and Analytical Chemistry, and Structural Chemistry, Merck Research Laboratories, P O Box 4, Sumneytown Pike, West Point, Pennsylvania 19486, United States
ACS Med Chem Lett 7:312-7. 2016....
- Discovery and Optimization of a Series of Pyrimidine-Based Phosphodiesterase 10A (PDE10A) Inhibitors through Fragment Screening, Structure-Based Design, and Parallel SynthesisWilliam D Shipe
Departments of Discovery Chemistry, Chemistry Modeling and Informatics, Neuroscience, and Structural Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, United States
J Med Chem 58:7888-94. 2015..Compound 15 h, with PDE10A Ki of 8.2 pM, LE of 0.49, and >5000-fold selectivity over other PDEs, fully attenuates MK-801-induced hyperlocomotor activity after ip dosing...
- Subthalamic nucleus lesions enhance the psychomotor-activating, incentive motivational, and neurobiological effects of cocaineJason M Uslaner
Department of Psychology, University of Michigan, Ann Arbor, Michigan 48019 1109, USA
J Neurosci 25:8407-15. 2005..Thus, the STN may serve as a novel target for therapeutic interventions aimed at treating drug dependence...
- The mGluR7 allosteric agonist AMN082 produces antidepressant-like effects by modulating glutamatergic signalingStefania Risso Bradley
MRL Department of Neuroscience, Merck and Co, Inc, West Point, PA, USA
Pharmacol Biochem Behav 101:35-40. 2012..Therefore, our findings confirm the hypothesis that mGluR7 could represent a novel target for treating depression...
- Behavioral and qEEG effects of the PDE10A inhibitor THPP-1 in a novel rhesus model of antipsychotic activityJoshua D Vardigan
Merck and Co, Inc, WP45 1114, 770 Sumneytown Pike, West Point, PA, 19486, USA
Psychopharmacology (Berl) 233:2441-50. 2016..However, concerns persist regarding the clinical translatability of these models for newer drug classes like PDE10A inhibitors...
- Improved cognition without adverse effects: novel M1 muscarinic potentiator compares favorably to donepezil and xanomeline in rhesus monkeyJoshua D Vardigan
Merck and Co, Inc, WP44E 200 770 Sumneytown Pike, West Point, PA, 19486, USA
Psychopharmacology (Berl) 232:1859-66. 2015..Therefore, there is an unmet medical need for a symptomatic treatment that improves symptoms and is better tolerated...
- Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulatorsAnthony L Gotter
Department of Neuroscience, Merck Research Laboratories, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486 0004, USA
BMC Neurosci 15:109. 2014..The current study compares the role and interdependence of these two mechanisms on their ability to influence sleep architecture and quantitative electroencephalography (qEEG) spectral profiles across preclinical species...
- The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 attenuates a scopolamine-induced deficit in a novel rodent attention taskJoshua D Vardigan
In Vivo Pharmacology, Merck and Co, Inc, West Point, PA 19486, USA
J Neurogenet 25:120-6. 2011..These data confirm and extend the hypothesis that PDE9 inhibition might serve as a novel treatment for AD and age-related cognitive decline...
- 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead effortsEdward J Brnardic
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
Bioorg Med Chem Lett 20:3129-33. 2010..An optimized lead compound was found to be brain penetrant and active in a rat ketamine-induced hyperlocomotion model for antipsychotic activity...
- The attribution of incentive salience to a stimulus that signals an intravenous injection of cocaineJason M Uslaner
Biopsychology and Neuroscience Programs, Department of Psychology, The University of Michigan, Ann Arbor, MI 48019 1109, USA
Behav Brain Res 169:320-4. 2006..Delineating the neurobiological mechanisms responsible for this process will be important for understanding and treating drug addiction...
- The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse modelVanita Puri
Merck Research Laboratories, West Point, PA, USA Electronic address
Behav Brain Res 287:96-9. 2015....
- Mechanism based neurotoxicity of mGlu5 positive allosteric modulators--development challenges for a promising novel antipsychotic targetSophie Parmentier-Batteur
Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486 0004, USA Electronic address
Neuropharmacology 82:161-73. 2014..This study reveals for the first time that augmentation of mGlu5 function with selective allosteric modulators results in neurotoxicity...
- The M1 Muscarinic Positive Allosteric Modulator PQCA Improves Performance on Translatable Tests of Memory and Attention in Rhesus MonkeysHenry S Lange
Merck and Co, Inc, West Point, Pennsylvania
J Pharmacol Exp Ther 355:442-50. 2015..These results further suggest that M1-positive allosteric modulators, either as monotherapy or as an add-on to current standards of care, have potential to reduce the cognitive deficits associated with AD. ..
- Methamphetamine-induced structural plasticity in the dorsal striatumJakub P Jedynak
Neuroscience Program, The University of Michigan, Ann Arbor, MI, USA
Eur J Neurosci 25:847-53. 2007....
- Discovery of 5-aryl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones as positive allosteric modulators of metabotropic glutamate subtype-2 (mGlu2) receptors with efficacy in a preclinical model of psychosisMark E Layton
Department of Medicinal Chemistry, Merck Research Laboratories, P O Box 4, Sumneytown Pike, West Point, PA 19486, United States
Bioorg Med Chem Lett 26:1260-4. 2016..Gratifyingly, compound 27 showed full efficacy in the PCP- and MK-801-induced hyperlocomotion assay in rats at CSF concentrations consistent with mGlu2 PAM potency. ..
- The Therapeutic Potential of D-Amino Acid Oxidase (DAAO) InhibitorsSean M Smith
Merck and Co, Inc, West Point, PA, USA
Open Med Chem J 4:3-9. 2010..This article highlights and reviews research advances for DAAO inhibitors published in peer reviewed journals...
- fMRI study of olfaction in the olfactory bulb and high olfactory structures of rats: Insight into their roles in habituationFuqiang Zhao
Merck and Co, Inc, West Point, PA 19486, USA Electronic address
Neuroimage 127:445-55. 2016..These results support previous reports that HOR plays a more significant role than OB in olfactory habituation. The technical approach presented in this study should enable more extensive fMRI studies of olfactory processing in rats. ..
- Amphetamine-induced c-fos mRNA expression in the caudate-putamen and subthalamic nucleus: interactions between dose, environment, and neuronal phenotypeJason M Uslaner
Biopsychology and Neuroscience Programs, Department of Psychology, The University of Michigan, Ann Arbor, Michigan 48019, USA
J Neurochem 85:105-14. 2003....