Research Topics
Genomes and GenesSpecies | G A HigginsSummaryAffiliation: Schering-Plough Research Institute Country: USA Publications
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Publications
Transgenic mouse models of Alzheimer's disease: phenotype and applicationGuy A Higgins
Schering Plough Research Institute, Kenilworth, New Jersey, USA
Behav Pharmacol 14:419-38. 2003..The review also considers the role behavioural testing may have in future AD drug discovery research...- The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonismGuy A Higgins
PRBN, F Hoffmann La Roche Ltd, Basel, Switzerland
Psychopharmacology (Berl) 170:309-19. 2003..The 5-HT(2C) receptor antagonist SB242,084 failed to exert equivalent effects, rather a trend toward exacerbation of the behavioural changes produced by dizocilpine was apparent... - Serotonin and drug reward: focus on 5-HT2C receptorsGuy A Higgins
Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Eur J Pharmacol 480:151-62. 2003..Finally, we consider the potential for selective 5-HT(2C) agonists as therapies for substance abuse disorders and the medical implications for different 5-HT(2C) receptor isoforms generated by RNA editing... - Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63-1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibitionG A Higgins
PRBN, F Hoffmann La Roche Ltd, Basel, Switzerland
Neuropharmacology 44:324-41. 2003..However, in the 5-CSRT and DRL24 tasks, Ro 63-1908 produced behaviours suggestive of impaired response inhibition, implicating a critical role of NMDA NR2B transmission in this process... - Donepezil reverses a mnemonic deficit produced by scopolamine but not by perforant path lesion or transient cerebral ischaemiaG A Higgins
PRBN, F Hoffmann La Roche AG, Basel, Switzerland
Eur J Neurosci 15:1827-40. 2002..The results are considered in terms of the effectiveness of acetylcholinesterase inhibitors in noncholinergic-based preclinical cognitive models... - Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological functionG A Higgins
Pharma Research Basel Neuroscience, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
Neuropharmacology 41:97-107. 2001.... 
Influence of the 5-HT(2C) receptor antagonist SB242,084 on behaviour produced by the 5-HT(2) agonist Ro60-0175 and the indirect 5-HT agonist dexfenfluramineG A Higgins
PRBN-B, F. Hoffmann-La Roche Ltd, CH-4070, Basel, Switzerland
Br J Pharmacol 133:459-66. 2001..An attenuation of the hyperlocomotor response was also observed following MDL100,907. These findings suggest that 5-HT(2C) receptor activation can inhibit the expression of behaviours mediated through other 5-HT receptor subtypes...- Comparison of the V1b antagonist, SSR149415, and the CRF1 antagonist, CP-154,526, in rodent models of anxiety and depressionR A Hodgson
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
Pharmacol Biochem Behav 86:431-40. 2007..This work demonstrates the different profiles of V1b and CRF1 receptor antagonists and supports both approaches in the treatment of affective disorders... - Effect of LSD on prepulse inhibition and spontaneous behavior in the rat. A pharmacological analysis and comparison between two rat strainsA Ouagazzal
Pharmaceuticals Division, Preclinical Studies, F Hoffmann La Roche, Basel, Switzerland
Neuropsychopharmacology 25:565-75. 2001..These findings provide empirical evidence to support the view that the hallucinogenic effects of LSD are mediated by a direct agonist effect at 5-HT(2A) receptors... - A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memoryG A Higgins
PRBN, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
Eur J Neurosci 15:911-22. 2002..This is consistent with a likely modulatory role of OFQ/N on hippocampal and associated cortical circuitry... - The alpha4beta2 agonist SIB 1765F, but not the alpha7 agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotineA J Grottick
Pharma Division, F Hoffman La Roche AG, Basel, Switzerland
Psychopharmacology (Berl) 150:233-6. 2000..Although studies have begun to identify the nicotinic receptor subtype(s) mediating the psychostimulant properties of nicotine, none as yet have investigated the subtypes which contribute to the process of sensitisation... - Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple speciesG B Varty
Department of Neurobiology, K 15 2600, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Psychopharmacology (Berl) 182:132-43. 2005..Previous studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198... - Spatial and associative learning deficits induced by neonatal excitotoxic hippocampal damage in rats: further evaluation of an animal model of schizophreniaG Le Pen
Pharma Division, Preclinical CNS Research, F Hoffmann La Roche Ltd, Basel, Switzerland
Behav Pharmacol 11:257-68. 2000..Therefore, this neurodevelopmental model of schizophrenia seems to exhibit an interesting degree of validity in possibly simulating some cognitive impairments and sensorimotor gating deficits frequently observed in psychotic patients... - Activation of 5-HT(2C) receptors reduces the locomotor and rewarding effects of nicotineA J Grottick
PRBN-B, F. Hoffmann-La Roche Ltd, Basel, Switzerland
Psychopharmacology (Berl) 157:292-8. 2001..CONCLUSIONS: The present data support an involvement for the 5-HT(2C) receptor in mediating mesolimbic DA functioning as assessed by changes in behaviours indicative of nicotine reward... - Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK1 receptor antagonistT M Ballard
Preclinical CNS Research, PRBN B, Bau 72 149, F Hoffmann La Roche AG, CH 4070, Basel, Switzerland
Eur J Pharmacol 412:255-64. 2001..The data support a role for tachykinin NK1 receptor antagonists as novel anxiolytic/antidepressants... - Dopamine agonist-induced hypothermia and disruption of prepulse inhibition: evidence for a role of D3 receptors?G B Varty
Glaxo Unit for Behavioural Psychopharmacology, University of Hertfordshire, UK
Behav Pharmacol 9:445-55. 1998.... - Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared ratsG B Varty
Glaxo Unit of Behavioural Psychopharmacology, Division of Biosciences, University of Hertfordshire, Hatfield, Herts, UK
Brain Res 824:197-203. 1999..These preliminary studies extend the characterisation of isolation rearing as a model for the investigation of neurodevelopmental diseases such as schizophrenia... - Age-progressing cognitive impairments and neuropathology in transgenic CRND8 miceLynn A Hyde
Schering Plough Research Institute, NJ 07033, Kenilworth, USA
Behav Brain Res 160:344-55. 2005..Therefore compared to their Non-Tg littermates, Tg CRND8 mice demonstrate cognitive impairments that progressed with age and seemed to coincide with the onset of beta-amyloid plaque deposition... - 2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs as adenosine A2A antagonists: the successful reduction of hERG activity. Part 2Julius J Matasi
Department of Medicinal Chemistry-CV and CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 15:3675-8. 2005..As a result, compounds 21 and 24 possess excellent in vitro profiles, highly promising in vivo profiles, and acceptable levels of hERG channel inhibition... - Glutamate receptor subtypes: promising new pharmacotherapeutic targetsGuy A Higgins
Psychopharmacology (Berl) 179:1-3. 2005 - Evidence for improved performance in cognitive tasks following selective NR2B NMDA receptor antagonist pre-treatment in the ratGuy A Higgins
PRBN, F Hoffmann La Roche Ltd, Basel, Switzerland
Psychopharmacology (Berl) 179:85-98. 2005..We previously reported that the NR2B subunit-selective N-methyl-D-aspartate (NMDA) antagonist Ro 63-1908 produced a marked deficit in response control in the five-choice serial reaction time task (5-CSRTT)... - Enhancing effects of nicotine and impairing effects of scopolamine on distinct aspects of performance in computerized attention and working memory tasks in marmoset monkeysSimona Spinelli
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland
Neuropharmacology 51:238-50. 2006..These data are consistent with a dissociation of the roles of muscarinic and nicotinic cholinergic receptors in the regulation of both sustained attention and working memory in primates... - The effects of the 5-HT(2C) receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonistsPaul J Fletcher
Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
Psychopharmacology (Berl) 187:515-25. 2006..The 5-HT(2C) receptor may also be involved in drug-induced locomotion that is 5-HT-dependent... - Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouseLynn A Hyde
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
J Pharmacol Exp Ther 319:1133-43. 2006.... - The 5-HT2C receptor agonist Ro60-0175 reduces cocaine self-administration and reinstatement induced by the stressor yohimbine, and contextual cuesPaul J Fletcher
Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
Neuropsychopharmacology 33:1402-12. 2008..The effects of Ro60-0175 do not exhibit tolerance within the 8-day test period. These results indicate that selective 5-HT2C receptor agonists may be a useful pharmacological strategy for treatment of drug abuse... - Opposing effects of 5-HT(2A) and 5-HT(2C) receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time testPaul J Fletcher
Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada
Psychopharmacology (Berl) 195:223-34. 2007..Serotonin (5-HT) has been linked to impulsivity with recent data suggesting that different receptor sub-types exert opposing influences on this behaviour... - The effect of caffeine to increase reaction time in the rat during a test of attention is mediated through antagonism of adenosine A2A receptorsGuy A Higgins
Department of Neurobiology, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Behav Brain Res 185:32-42. 2007..Furthermore, the improvement in response control in amphetamine-treated rats following CGS-21680 pretreatment supports the view that A(2A) agonists have potential as novel antipsychotics... - The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profilesGeoffrey B Varty
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
Psychopharmacology (Berl) 179:207-17. 2005..Modulation of metabotropic glutamate receptor (mGluR) subtypes represents a novel approach for the treatment of neurological and psychiatric disorders... - PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammationJ Grayson Richards
Department of Pharma Research Biology Discovery and Roche Center for Medical Genomics, F Hoffmann La Roche Ltd, CH 4070 Basel, Switzerland
J Neurosci 23:8989-9003. 2003.... - Differential effects of the 5-HT(2A) receptor antagonist M100907 and the 5-HT(2C) receptor antagonist SB242084 on cocaine-induced locomotor activity, cocaine self-administration and cocaine-induced reinstatement of respondingPaul J Fletcher
Departments of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada
Neuropsychopharmacology 27:576-86. 2002..These results indicate distinct, and in some cases opposite, effects of a 5-HT(2A) compared with a 5-HT(2C) receptor antagonist on various cocaine-mediated behavioral effects... - Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligandsAndrew J Grottick
PRBN B, F Hoffmann La Roche AG, Basel, Switzerland
Neuropsychopharmacology 28:880-7. 2003..These results support a critical involvement for the alpha(4)beta(2) nicotinic receptor in mediating the attention-enhancing properties of nicotine... - Effect of the 5-HT6 receptor antagonists Ro04-6790 and Ro65-7199 on latent inhibition and prepulse inhibition in the rat: comparison to clozapineAndreas Leng
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603, Schwerzenbach, Switzerland
Pharmacol Biochem Behav 75:281-8. 2003..Since each of these tests bear some predictive validity for the detection of antipsychotic drugs, the present studies do not support a therapeutic potential of 5-HT6 receptor antagonists in this regard... - Severe impairment of NMDA receptor function in mice carrying targeted point mutations in the glycine binding site results in drug-resistant nonhabituating hyperactivityTheresa M Ballard
Preclinical CNS Research, F Hoffmann La Roche Limited, CH 4070 Basel, Switzerland
J Neurosci 22:6713-23. 2002..We speculate that the severity of NMDA receptor hypofunction in these mice may account for their profound behavioral phenotype and insensitivity to antipsychotics... - Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxietyJames R Martin
Neuroscience Department, Pharma Division, F Hoffmann La Roche Ltd, CH 4070, Basel, Switzerland
Pharmacol Biochem Behav 71:615-25. 2002..The present results demonstrate an anxiolytic potential of SB-242084, as well as an intrinsic response-enhancing property, however, both of these effects are task dependent... - Phencyclidine exacerbates attentional deficits in a neurodevelopmental rat model of schizophreniaGwenaëlle Le Pen
INSERM EMI 0117, Centre Paul Broca, Paris, France
Neuropsychopharmacology 28:1799-809. 2003..4-0.8 mg/kg) had a similar effect in control and VH-lesioned rats. Thus, NVH-lesioned rats were impaired in the acquisition of stable performance in the 5-CSRTT, and were hypersensitive to the cognitive-impairing effects of PCP... - Injection of the 5-HT2C receptor agonist Ro60-0175 into the ventral tegmental area reduces cocaine-induced locomotor activity and cocaine self-administrationPaul J Fletcher
Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
Neuropsychopharmacology 29:308-18. 2004..These effects complement electrophysiological and neurochemical findings, and indicate that 5-HT(2C) receptors localized within the VTA modulate the activity of mesolimbic DA neurons... - Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiationGwendolyn T Wong
Department of Central Nervous System Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
J Biol Chem 279:12876-82. 2004.... - Pharmacological and genetic evidence indicates that combined inhibition of NR2A and NR2B subunit containing NMDA receptors is required to disrupt prepulse inhibitionWill Spooren
F Hoffmann La Roche Ltd, Pharma Research Basel Discovery, Building 72 148, 4070 Basel, Switzerland
Psychopharmacology (Berl) 175:99-105. 2004.... - Performance of the marmoset monkey on computerized tasks of attention and working memorySimona Spinelli
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland
Brain Res Cogn Brain Res 19:123-37. 2004.... - Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodentGuy A Higgins
Preclinical CNS Research, F Hoffmann La Roche Ltd, PRBD N, 72 150, Grenzacherstrasse, CH 4070 Basel, Switzerland
Neuropharmacology 46:907-17. 2004..Conversely, mGlu2 receptor antagonists may improve certain aspects of cognition and thus represent a novel approach for the symptomatic treatment of AD... - Assessing a vigilance decrement in aged rats: effects of pre-feeding, task manipulation, and psychostimulantsAndrew J Grottick
PRBN B, F Hoffmann La Roche AG, 4070 Basel, Switzerland
Psychopharmacology (Berl) 164:33-41. 2002..The five-choice serial reaction time task (5-CSRTT) has been described as a test of sustained attention in the rat, however, studies describing vigilance decrements and performance effects of psychostimulants in this task are scarce... - The opioid receptor like-1 receptor agonist Ro 64-6198 (1S,3aS-8-2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one) produces a discriminative stimulus in rats distinct from that of a mu, kappa, and delta opioid receptor aMatthew D Recker
K15-2-2600, Schering Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
J Pharmacol Exp Ther 311:652-8. 2004..The present studies demonstrate that rats may be trained to discriminate Ro 64-6198 from saline, and the pharmacological characteristics of this cue are most consistent with ORL-1 receptor activation... - Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonistsTorsten Hoffmann
F Hoffmann La Roche Ltd, Pharma Research, CH 4070 Basel, Switzerland
Bioorg Med Chem Lett 16:1362-5. 2006..The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration... 
Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonistsUnmesh Shah
Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
Bioorg Med Chem Lett 18:4204-9. 2008....