G A Higgins

Summary

Affiliation: Schering-Plough Research Institute
Country: USA

Publications

  1. ncbi Transgenic mouse models of Alzheimer's disease: phenotype and application
    Guy A Higgins
    Schering Plough Research Institute, Kenilworth, New Jersey, USA
    Behav Pharmacol 14:419-38. 2003
  2. ncbi The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism
    Guy A Higgins
    PRBN, F Hoffmann La Roche Ltd, Basel, Switzerland
    Psychopharmacology (Berl) 170:309-19. 2003
  3. ncbi Serotonin and drug reward: focus on 5-HT2C receptors
    Guy A Higgins
    Schering Plough Research Institute, K15 2 2600, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Eur J Pharmacol 480:151-62. 2003
  4. ncbi Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63-1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibition
    G A Higgins
    PRBN, F Hoffmann La Roche Ltd, Basel, Switzerland
    Neuropharmacology 44:324-41. 2003
  5. ncbi Donepezil reverses a mnemonic deficit produced by scopolamine but not by perforant path lesion or transient cerebral ischaemia
    G A Higgins
    PRBN, F Hoffmann La Roche AG, Basel, Switzerland
    Eur J Neurosci 15:1827-40. 2002
  6. ncbi Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function
    G A Higgins
    Pharma Research Basel Neuroscience, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
    Neuropharmacology 41:97-107. 2001
  7. pmc 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 dexfenfluramine
    G A Higgins
    PRBN-B, F. Hoffmann-La Roche Ltd, CH-4070, Basel, Switzerland
    Br J Pharmacol 133:459-66. 2001
  8. ncbi Comparison of the V1b antagonist, SSR149415, and the CRF1 antagonist, CP-154,526, in rodent models of anxiety and depression
    R A Hodgson
    Department of Neurobiology, Schering Plough Research Institute, Kenilworth, NJ 07033, USA
    Pharmacol Biochem Behav 86:431-40. 2007
  9. ncbi Effect of LSD on prepulse inhibition and spontaneous behavior in the rat. A pharmacological analysis and comparison between two rat strains
    A Ouagazzal
    Pharmaceuticals Division, Preclinical Studies, F Hoffmann La Roche, Basel, Switzerland
    Neuropsychopharmacology 25:565-75. 2001
  10. ncbi A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory
    G A Higgins
    PRBN, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
    Eur J Neurosci 15:911-22. 2002

Collaborators

Detail Information

Publications44

  1. ncbi Transgenic mouse models of Alzheimer's disease: phenotype and application
    Guy 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...
  2. ncbi The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism
    Guy 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...
  3. ncbi Serotonin and drug reward: focus on 5-HT2C receptors
    Guy 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...
  4. ncbi Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63-1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibition
    G 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...
  5. ncbi Donepezil reverses a mnemonic deficit produced by scopolamine but not by perforant path lesion or transient cerebral ischaemia
    G 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...
  6. ncbi Influence of the selective ORL1 receptor agonist, Ro64-6198, on rodent neurological function
    G A Higgins
    Pharma Research Basel Neuroscience, F Hoffmann La Roche AG, CH 4070 Basel, Switzerland
    Neuropharmacology 41:97-107. 2001
    ....
  7. pmc 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 dexfenfluramine
    G 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...
  8. ncbi Comparison of the V1b antagonist, SSR149415, and the CRF1 antagonist, CP-154,526, in rodent models of anxiety and depression
    R 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...
  9. ncbi Effect of LSD on prepulse inhibition and spontaneous behavior in the rat. A pharmacological analysis and comparison between two rat strains
    A 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...
  10. ncbi A combined pharmacological and genetic approach to investigate the role of orphanin FQ in learning and memory
    G 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...
  11. ncbi The alpha4beta2 agonist SIB 1765F, but not the alpha7 agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotine
    A 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...
  12. ncbi Characterization of the nociceptin receptor (ORL-1) agonist, Ro64-6198, in tests of anxiety across multiple species
    G 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...
  13. ncbi Spatial and associative learning deficits induced by neonatal excitotoxic hippocampal damage in rats: further evaluation of an animal model of schizophrenia
    G 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...
  14. ncbi Activation of 5-HT(2C) receptors reduces the locomotor and rewarding effects of nicotine
    A 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...
  15. ncbi Inhibition of shock-induced foot tapping behaviour in the gerbil by a tachykinin NK1 receptor antagonist
    T 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...
  16. ncbi 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
    ....
  17. ncbi Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats
    G 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...
  18. ncbi Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice
    Lynn 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...
  19. ncbi 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 2
    Julius 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...
  20. ncbi Glutamate receptor subtypes: promising new pharmacotherapeutic targets
    Guy A Higgins
    Psychopharmacology (Berl) 179:1-3. 2005
  21. ncbi Evidence for improved performance in cognitive tasks following selective NR2B NMDA receptor antagonist pre-treatment in the rat
    Guy 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)...
  22. ncbi Enhancing effects of nicotine and impairing effects of scopolamine on distinct aspects of performance in computerized attention and working memory tasks in marmoset monkeys
    Simona 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...
  23. ncbi The effects of the 5-HT(2C) receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists
    Paul 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...
  24. ncbi 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 mouse
    Lynn A Hyde
    Department of Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
    J Pharmacol Exp Ther 319:1133-43. 2006
    ....
  25. ncbi The 5-HT2C receptor agonist Ro60-0175 reduces cocaine self-administration and reinstatement induced by the stressor yohimbine, and contextual cues
    Paul 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...
  26. ncbi 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 test
    Paul 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...
  27. ncbi The effect of caffeine to increase reaction time in the rat during a test of attention is mediated through antagonism of adenosine A2A receptors
    Guy 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...
  28. ncbi 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 profiles
    Geoffrey 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...
  29. ncbi PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation
    J 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
    ....
  30. ncbi 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 responding
    Paul 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...
  31. ncbi Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligands
    Andrew 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...
  32. ncbi Effect of the 5-HT6 receptor antagonists Ro04-6790 and Ro65-7199 on latent inhibition and prepulse inhibition in the rat: comparison to clozapine
    Andreas 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...
  33. ncbi Severe impairment of NMDA receptor function in mice carrying targeted point mutations in the glycine binding site results in drug-resistant nonhabituating hyperactivity
    Theresa 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...
  34. ncbi Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety
    James 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...
  35. ncbi Phencyclidine exacerbates attentional deficits in a neurodevelopmental rat model of schizophrenia
    Gwenaƫlle 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...
  36. ncbi Injection of the 5-HT2C receptor agonist Ro60-0175 into the ventral tegmental area reduces cocaine-induced locomotor activity and cocaine self-administration
    Paul 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...
  37. ncbi Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation
    Gwendolyn 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
    ....
  38. ncbi Pharmacological and genetic evidence indicates that combined inhibition of NR2A and NR2B subunit containing NMDA receptors is required to disrupt prepulse inhibition
    Will Spooren
    F Hoffmann La Roche Ltd, Pharma Research Basel Discovery, Building 72 148, 4070 Basel, Switzerland
    Psychopharmacology (Berl) 175:99-105. 2004
    ....
  39. ncbi Performance of the marmoset monkey on computerized tasks of attention and working memory
    Simona 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
    ....
  40. ncbi Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent
    Guy 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...
  41. ncbi Assessing a vigilance decrement in aged rats: effects of pre-feeding, task manipulation, and psychostimulants
    Andrew 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...
  42. ncbi 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 a
    Matthew 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...
  43. ncbi Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists
    Torsten 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...
  44. doi Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists
    Unmesh Shah
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA
    Bioorg Med Chem Lett 18:4204-9. 2008
    ....