In vitro and in vivo characterisation of Lu AF64280, a novel, brain penetrant phosphodiesterase (PDE) 2A inhibitor: Potential relevance to cognitive deficits in schizophrenia

Psychopharmacology

Volumn 231, Issue 16, 2014, Pages 3151-3167

  Redrobe, John P ^a   Jørgensen, Morten ^a   Christoffersen, Claus T ^a   Montezinho, Liliana P ^a   Bastlund, Jesper F ^a   Carnerup, Martin ^a   Bundgaard, Christoffer ^a   Lerdrup, Linda ^a   Plath, Niels ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

Animal model; Antipsychotic; Behaviour; Cognition; Cyclic GMP; Phosphodiesterase 2a; Schizophrenia

Indexed keywords

CYCLIC GMP; HALOPERIDOL; LU AF 64280; MODAFINIL; PHENCYCLIDINE DERIVATIVE; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; RECOMBINANT ENZYME; UNCLASSIFIED DRUG; AMINO ACID RECEPTOR BLOCKING AGENT; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 2; FUSED HETEROCYCLIC RINGS; LU AF64280; NEUROLEPTIC AGENT; PHENCYCLIDINE; RECOMBINANT PROTEIN;

ANALYSIS OF VARIANCE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIPSYCHOTIC ACTIVITY; ARTICLE; AUDITORY GATING; AVOIDANCE BEHAVIOR; BRAIN HOMOGENATE; COGNITION; COGNITIVE DEFECT; CONTROLLED STUDY; DISEASE ASSOCIATION; DOSE RESPONSE; DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG STRUCTURE; DRUG TISSUE LEVEL; ENZYME INHIBITION; FEMALE; HIPPOCAMPUS; HYPERACTIVITY; IN VITRO STUDY; IN VIVO STUDY; MALE; MENTAL TASK; MICRODIALYSIS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FOLDING; RAT; SCHIZOPHRENIA; SENSORY GATING; TREATMENT FAILURE; ANIMAL; ANIMAL BEHAVIOR; ANTAGONISTS AND INHIBITORS; CHEMICALLY INDUCED; COGNITION DISORDERS; COMPLICATION; DBA MOUSE; DRUG EFFECTS; HUMAN; HYPERKINESIS; METABOLISM; PSYCHOLOGY; RECOGNITION;

ANIMALS; ANTIPSYCHOTIC AGENTS; AVOIDANCE LEARNING; BEHAVIOR, ANIMAL; COGNITION DISORDERS; CYCLIC GMP; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 2; EXCITATORY AMINO ACID ANTAGONISTS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HIPPOCAMPUS; HUMANS; HYPERKINESIS; MALE; MICE; MICE, INBRED DBA; PHENCYCLIDINE; PHOSPHODIESTERASE INHIBITORS; RATS; RECOGNITION (PSYCHOLOGY); RECOMBINANT PROTEINS; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY; SENSORY GATING;

EID: 84904961034     PISSN: 00333158     EISSN: 14322072     Source Type: Journal    
DOI: 10.1007/s00213-014-3492-7     Document Type: Article

References (96)

1. Adams CE, Stitzel JA, Collins AC, Freedman R (2001) Alpha7-nicotinic receptor expression and the anatomical organization of hippocampal interneurons. Brain Res 922:180-190
2. Aleman A, Hijman R, de Haan EH, Kahn RS (1999) Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry 156:1358-1366
3. Bayer SA, Altman J, Russo RJ, Zhang X (1993) Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicology 14:83-144
4. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58:488-520
5. Berg EA (1948) A simple objective technique for measuring flexibility in thinking. J Gen Psychol 39:15-22
6. Birrell JM, Brown VJ (2000) Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20:4320-4324
7. Boess FG, Hendrix M, van der Staay FJ, Erb C, Schreiber R, van Staveren W, de Vente J, Prickaerts J, Blokland A, Koenig G (2004) Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance. Neuropharmacology 47:1081-1092
8. Bolger GB, Rodgers L, Riggs M (1994) Differential CNS expression of alternative mRNA isoforms of the mammalian genes encoding cAMP-specific phosphodiesterases. Gene 149:237-244
9. Breese CR, Adams C, Logel J, Drebing C, Rollins Y, Barnhart M, Sullivan B, Demasters BK, Freedman R, Leonard S (1997) Comparison of the regional expression of nicotinic acetylcholine receptor alpha7 mRNA and [125I]-alpha-bungarotoxin binding in human postmortem brain. J Comp Neurol 387:385-398
10. Broberg BV, Dias R, Glenthøj BY, Olsen CK (2008) Evaluation of a neurodevelopmental model of schizophrenia - early postnatal PCP treatment in attentional set-shifting. Behav Brain Res 190:160-163
11. Broberg BV, Glenthøj BY, Dias R, Larsen DB, Olsen CK (2009) Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia: sub-chronic and early postnatal PCP treatment in attentional set-shifting. Psychopharmacology 206:631-640
12. Chini B, Raimond E, Elgoyhen AB, Moralli D, Balzaretti M, Heinemann S (1994) Molecular cloning and chromosomal localization of the human alpha 7-nicotinic receptor subunit gene (CHRNA7). Genomics 19:379-381
13. Clancy B, Darlington RB, Finlay BL (2001) Translating developmental time across mammalian species. Neuroscience 105:7-17
14. Clare L, McKenna PJ, Mortimer AM, Baddeley AD (1993) Memory in schizophrenia: what is impaired and what is preserved? Neuropsychologia 31:1225-1241
15. Clark RE, Zola SM, Squire LR (2000) Impaired recognition memory in rats after damage to the hippocampus. J Neurosci 20:8853-8860
16. Cutshall NS, Onrust R, Rohde A, Gragerov S, Hamilton L, Harbol K, Shen HR, McKee S, Zuta C, Gragerova G, Florio V, Wheeler TN, Gage JL (2012) Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia. Bioorg Med Chem Lett 22:5595-5599
17. Damgaard T, Larsen DB, Hansen SL, Grayson B, Neill JC, Plath N (2010) Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats. Behav Brain Res 207:144-150
18. Deutsch SI, Mastropaolo J, Rosse RB (1998) Neurodevelopmental consequences of early exposure to phencyclidine and related drugs. Clin Neuropharmacol 21:320-332
19. Do J, Kim JI, Bakes J, Lee K, Kaang BK (2012) Functional roles of neurotransmitters and neuromodulators in the dorsal striatum. Learn Mem 20:21-28
20. Elliott R, McKenna PJ, Robbins TW, Sahakian BJ (1995) Neuropsychological evidence for frontostriatal dysfunction in schizophrenia. Psychol Med 25:619-626
21. Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioural data. Behav Brain Res 31:47-59
22. Fett AK, Viechtbauer W, Dominguez MD, Penn DL, van Os J, Krabbendam L (2011) The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 35:573-588
23. Freedman R, Hall M, Adler LE, Leonard S (1995) Evidence in postmortem brain tissue for decreased numbers of hippocampal nicotinic receptors in schizophrenia. Biol Psychiatry 38:22-33
24. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams C, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci U S A 94:587-592
25. Freedman R, Adams CE, Adler LE, Bickford PC, Gault J, Harris JG, Nagamoto HT, Olincy A, Ross RG, Stevens KE, Waldo M, Leonard S (2000) Inhibitory neurophysiological deficit as a phenotype for genetic investigation of schizophrenia. Am J Med Genet 97:58-64
26. Goetghebeur P, Dias R (2009) Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set-shifting impairment following subchronic PCP administration in the rat: a back translational study. Psychopharmacology 202:287-293
27. Goetghebeur PJ, Lerdrup L, Sylvest A, Dias R (2010) Erythropoietin reverses the attentional set-shifting impairment in a rodent schizophrenia disease-like model. Psychopharmacology 212:635-642
28. Green MF, Bracha HS, Satz P, Christenson CD (1994) Preliminary evidence for an association between minor physical anomalies and second trimester neurodevelopment in schizophrenia. Psychiatry Res 53:119-127
29. Green MF, Kern RS, Heaton RK (2004) Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res 72:41-51
30. Harvey PD, Keefe RSE (2001) Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 158:176-184
31. Haut MW, Cahill J, Cutlip WD, Stevenson JM, Makela EH, Bloomfield SM (1996) On the nature of Wisconsin card sorting test performance in schizophrenia. Psychiatry Res 65:15-22
32. Heckers S, Curran T, Goff D, Rauch SL, Fischman AJ, Alpert NM, Schacter DL (2000) Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia. Biol Psychiatry 48:651-657
33. Helal CJ, Kang Z, Hou X, Pandit J, Chappie TA, Humphrey JM, Marr ES, Fennell KF, Chenard LK, Fox C, Schmidt CJ, Williams RD, Chapin DS, Siuciak J, Lebel L, Menniti F, Cianfrogna J, Fonseca KR, Nelson FR, O'Connor R, MacDougall M, McDowell L, Liras S (2011) Use of structure-based design to discover a potent, selective, in vivo active phosphodiesterase 10A inhibitor lead series for the treatment of schizophrenia. J Med Chem 54:4536-4547
34. Hertel P, Didriksen M, Pouzet B, Brennum LT, Søby KK, Larsen AK, Christoffersen CT, Ramirez T, Marcus MM, Svensson TH, Di Matteo V, Esposito E, Bang-Andersen B, Arnt J (2007) Lu 35-138 ((+)-(S)-3-{1-[2-(1-acetyl-2,3-dihydro- 1H-indol-3-yl)ethyl]-3,6-dihydro-2H-pyridin-4-yl}-6-chloro-1H-indole), a dopamine D4 receptor antagonist and serotonin reuptake inhibitor: characterisation of its in vitro profile and pre-clinical antipsychotic potential. Eur J Pharmacol 573:148-160
35. Hu Y, Wu DL, Luo CX, Zhu LJ, Zhang J, Wu HY, Zhu DY (2012) Hippocampal nitric oxide contributes to sex difference in affective behaviors. Proc Natl Acad Sci U S A 109:14224-14229
36. Hutton SB, Puri BK, Duncan LJ, Robbins TW, Barnes TRE, Joyce EM (1998) Executive function in first-episode schizophrenia. Psychol Med 28:463-473
37. Idris N, Neill J, Grayson B, Bang-Andersen B, Witten LM, Brennum LT, Arnt J (2010) Sertindole improves sub-chronic PCP-induced reversal learning and episodic memory deficits in rodents: involvement of 5-HT(6) and 5-HT(2A) receptor mechanisms. Psychopharmacology 208:23-36
38. Jentsch JD, Roth RH (1999) The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20:201-225
39. Kalvass JC, Maurer TS (2002) Influence of nonspecific brain and plasma binding on CNS exposure: implications for rational drug discovery. Biopharm Drug Dispos 23:327-338
40. Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA, CATIE Investigators, Neurocognitive Working Group (2007) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE trial. Arch Gen Psychiatry 64:633-647
41. Kelly MP, Adamowicz W, Bove S, Hartman AJ, Mariga A, Pathak G, Reinhart V, Romegialli A, Kleiman RJ (2014) Select 3,5-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain. Cell Signal 26:383-397
42. Kleppisch T (2009) Phosphodiesterases in the central nervous system. Handb Exp Pharmacol 191:71-92
43. Kleppisch T, Feil R (2009) cGMP signalling in the mammalian brain: role in synaptic plasticity and behaviour. Handb Exp Pharmacol 191:549-579
44. Leeson VC, Robbins TW, Matheson E, Hutton SB, Ron MA, Barnes TR, Joyce EM (2009) Discrimination learning, reversal, and set-shifting in first-episode schizophrenia: stability over six years and specific associations with medication type and disorganization syndrome. Biol Psychiatry 66:586-593
45. Lucas KA, Pitari GM, Kazerounian S, Ruiz-Stewart I, Park J, Schulz S, Chepenik KP, Waldman SA (2000) Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev 52:375-414
46. Manns JR, Stark CEL, Squire LR (2000) The visual paired-comparison task as a measure of declarative memory. Proc Natl Acad Sci U S A 97:12375-12379
47. Masood A, Huang Y, Hajjhussein H, Xiao L, Li H, Wang W, Hamza A, Zhan CG, O'Donnell JM (2009) Anxiolytic effects of phosphodiesterase-2 inhibitors associated with increased cGMP signaling. J Pharmacol Exp Ther 331:690-699
48. McLean SL, Beck JP, Woolley ML, Neill JC (2008) A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats. Behav Brain Res 189:152-158
49. McLean SL, Grayson B, Idris NF, Lesage AS, Pemberton DJ, Mackie C, Neill JC (2010) Activation of alpha7 nicotinic receptors improves phencyclidine- induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia. Eur Neuropsychopharmacol 21:333-343
50. Miller CL, Freedman R (1995) The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated auditory stimuli. Neuroscience 69:371-381
51. Murray GK, Cheng F, Clark L, Barnett JH, Blackwell AD, Fletcher PC, Robbins TW, Bullmore ET, Jones PB (2008) Reinforcement and reversal learning in first-episode psychosis. Schizophr Bull 34:848-855
52. Neill JC, Barnes S, Cook S, Grayson B, Idris NF, McLean SL, Snigdha S, Rajagopal L, Harte MK (2010) Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol Ther 128:419-432
53. O'Tuathaigh CM, Waddington JL (2010) Mutant mouse models: phenotypic relationships to domains of psychopathology and pathobiology in schizophrenia. Schizophr Bull 36:243-245
54. Orr-Urtreger A, Seldin MF, Baldini A, Beaudet AL (1995) Cloning and mapping of the mouse alpha 7-neuronal nicotinic acetylcholine receptor. Genomics 26:399-402
55. Pantelis C, Barber FZ, Barnes TR, Nelson HE, Owen AM, Robbins TW (1999) Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage. Schizophr Res 37:251-270
56. Paxinos G and Franklin K (2001) Paxinos and Franklin's the mouse brain in stereotaxic coordinates. Second edition, Academic Press, San Diego
57. Pedersen CS, Goetghebeur P, Dias R (2009) Chronic infusion of PCP via osmotic mini-pumps: a new rodent model of cognitive deficit in schizophrenia characterized by impaired attentional set-shifting (ID/ED) performance. J Neurosci Methods 185:66-69
58. Plummer MS, Cornicelli J, Roark H, Skalitzky DJ, Stankovic CJ, Bove S, Pandit J, Goodman A, Hicks J, Shahripour A, Beidler D, Lu XK, Sanchez B, Whitehead C, Sarver R, Braden T, Gowan R, Shen XQ, Welch K, Ogden A, Sadagopan N, Baum H, Miller H, Banotai C, Spessard C, Lightle S (2013) Discovery of potent selective bioavailable phosphodiesterase 2 (PDE2) inhibitors active in an osteoarthritis pain model. Part II: Optimization studies and demonstration of in vivo efficacy. Bioorg Med Chem Lett 23:3443-3447
59. Redrobe JP, Bull S, Plath N (2010) Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP): effects of modafinil and relevance to cognitive deficits in schizophrenia. Front Psychiatry 1:146
60. Redrobe JP, Elster L, Frederiksen K, Bundgaard C, de Jong IE, Smith GP, Bruun AT, Larsen PH, Didriksen M (2012) Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats. Psychopharmacology 221:451-468
61. Reneerkens OA, Rutten K, Steinbusch HW, Blokland A, Prickaerts J (2009) Selective phosphodiesterase inhibitors: a promising target for cognition enhancement. Psychopharmacology 202:419-443
62. Reneerkens OA, Rutten K, Bollen E, Hage T, Blokland A, Steinbusch HW, Prickaerts J (2013) Inhibition of phoshodiesterase type 2 or type 10 reverses object memory deficits induced by scopolamine or MK-801. Behav Brain Res 236:16-22
63. Repaske DR, Swinnen JV, Jin SL, Van Wyk JJ, Conti M (1992) A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning of the cDNA encoding the 63-kDa calmodulin-dependent phosphodiesterase. J Biol Chem 267:18683-18688
64. Reyes-Irisarri E, Markerink-Van Ittersum M, Mengod G, de Vente J (2007) Expression of the cGMP-specific phosphodiesterases 2 and 9 in normal and Alzheimer's disease human brains. Eur J Neurosci 25:3332-3338
65. Rodefer JS, Murphy ER, Baxter MG (2005) PDE10A inhibition reverses PCP-induced deficits in attentional set-shifting in rats. Eur J Neurosci 21:1070-1076
66. Rodefer JS, Nguyen TN, Karlsson JJ, Arnt J (2008) Reversal of subchronic PCP-induced deficits in attentional set shifting in rats by sertindole and a 5-HT6 receptor antagonist: comparison among antipsychotics. Neuropsychopharmacology 33:2657-2666
67. Rodefer JS, Saland SK, Eckrich SJ (2012) Selective phosphodiesterase inhibitors improve performance on the ED/ID cognitive task in rats. Neuropharmacology 62:1182-1190
68. Rosman GJ, Martins TJ, Sonnenburg WK, Beavo JA, Ferguson K, Loughney K (1997) Isolation and characterization of human cDNAs encoding a cGMP-stimulated 3,5-cyclic nucleotide phosphodiesterase. Gene 191:89-95
69. Sadhu K, Hensley K, Florio VA, Wolda SL (1999) Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. J Histochem Cytochem 47:895-906
70. Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW (1988) A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain 111:695-718
71. Schmidt CJ (2010) Phosphodiesterase inhibitors as potential cognition enhancing agents. Curr Top Med Chem 10:222-230
72. Seeger TF, Bartlett B, Coskran TM, Culp JS, James LC, Krull DL, Lanfear J, Ryan AM, Schmidt CJ, Strick CA, Varghese AH, Williams RD, Wylie PG, Menniti FS (2003) Immunohistochemical localization of PDE10A in the rat brain. Brain Res 985:113-126
73. Sharma T, Antonova L (2003) Cognitive function in schizophrenia: deficits, functional consequences, and future treatment. Psychiatr Clin North Am 26:25-40
74. Singer P, Feldon J, Yee BK (2009) Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice. Psychopharmacology 206:677-698
75. Smith SM, Uslaner JM, Cox CD, Huszar SL, Cannon CE, Vardigan JD, Eddins D, Toolan DM, Kandebo M, Yao L, Raheem IT, Schreier JD, Breslin MJ, Coleman PJ, Renger JJ (2013) The novel phosphodiesterase 10A inhibitor THPP-1 has antipsychotic-like effects in rat and improves cognition in rat and rhesus monkey. Neuropharmacology 64:215-223
76. Snigdha S, Horiguchi M, Huang M, Li Z, Shahid M, Neill JC, Meltzer HY (2010) Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimivanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther 332:622-631
77. Sonnenburg WK, Mullaney PJ, Beavo JA (1991) Molecular cloning of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase cDNA. Identification and distribution of isozyme variants. J Biol Chem 266:17655-17661
78. Sotty F, Damgaard T, Montezinho LP, Mørk A, Olsen CK, Bundgaard C, Husum H (2009a) Antipsychotic-like effect of retigabine [N-(2-amino-4- (fluorobenzylamino)-phenyl)carbamic acid ester], a KCNQ potassium channel opener, via modulation of mesolimbic dopaminergic neurotransmission. J Pharmacol Exp Ther 328:951-962
79. Sotty F, Montezinho LP, Steiniger-Brach B, Nielsen J (2009b) Phosphodiesterase 10A inhibition modulates the sensitivity of the mesolimbic dopaminergic system to D-amphetamine: involvement of the D1-regulated feedback control of midbrain dopamine neurons. J Neurochem 109:766-775
80. Stephenson DT, Coskran TM, Wilhelms MB, Adamowicz WO, O'Donnell MM, Muravnick KB, Menniti FS, Kleiman RJ, Morton D (2009) Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J Histochem Cytochem 57:933-949
81. Stephenson DT, Coskran TM, Kelly MP, Kleiman RJ, Morton D, O'Neill SM, Schmidt CJ, Weinberg RJ, Menniti FS (2012) The distribution of phosphodiesterase 2A in the rat brain. Neuroscience 226:145-155
82. Stevens KE, Wear KD (1997) Normalizing effects of nicotine and a novel nicotinic agonist on hippocampal auditory gating in two animal models. Pharmacol Biochem Behav 57:869-874
83. Stevens KE, Freedman R, Collins AC, Hall M, Leonard S, Marks MJ, Rose GM (1996) Genetic correlation of inhibitory gating of hippocampal auditory evoked response and alpha-bungarotoxin-binding nicotinic cholinergic receptors in inbred mouse strains. Neuropsychopharmacology 15:152-162
84. Street LJ, Sternfeld F, Jelley RA, Reeve AJ, Carling RW, Moore KW, McKernan RM, Sohal B, Cook S, Dawson GR, Bromidge FA, Wafford KA, Seabrook GR, Thompson SA, Marshall G, Pillai GV, Castro JL, Atack JR, MacLeod AM (2004) Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10- ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site. J Med Chem 47:3642-3657
85. Tek C, Gold J, Blaxton T, Wilk C, McMahon RP, Buchanan RW (2002) Visual perceptual and working memory impairments in schizophrenia. Arch Gen Psychiatry 59:146-153
86. Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ (2004) Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology 29:1363-1373
87. Urgaonkar S, Verkade JG (2004) Palladium/proazaphosphatrane-catalyzed amination of aryl halides possessing a phenol, alcohol, acetanilide, amide or an enolizable ketone functional group: efficacy of lithium bis(trimethylsilyl) amide as the base. Adv Synth Catal 346:611-616
88. van Donkelaar EL, Rutten K, Blokland A, Akkerman S, Steinbusch HW, Prickaerts J (2008) Phosphodiesterase 2 and 5 inhibition attenuates the object memory deficit induced by acute tryptophan depletion. Eur J Pharmacol 600:98-104
89. van Staveren WC, Steinbusch HW, Markerink-Van Ittersum M, Repaske DR, Goy MF, Kotera J, Omori K, Beavo JA, De Vente J (2003) mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain. J Comp Neurol 467:566-580
90. van Staveren WC, Steinbusch HW, Markerink-van Ittersum M, Behrends S, de Vente J (2004) Species differences in the localization of cGMP-producing and NO-responsive elements in the mouse and rat hippocampus using cGMP immunocytochemistry. Eur J Neurosci 19:2155-2168
91. Wadenberg ML (2010) Conditioned avoidance response in the development of new antipsychotics. Curr Pharm Des 16:358-370
92. Westerink BHC, Damsma G, Rollema H, de Vries JB, Horn AS (1987) Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. Life Sci 41:1763-1776
93. Willott JF, Demuth RM, Lu SM, van Bergem P (1982) Abnormal tonotopic organization in the ventral cochlear nucleus of the hearing-impaired DBA/2 mouse. Neurosci Lett 34:13-17
94. Wilson C, Terry AV Jr (2010) Neurodevelopmental animal models of schizophrenia: role in novel drug discovery and development. Clin Schizophr Relat Psychoses 4:124-137
95. Xu Y, Zhang HT, O'Donnell JM (2011) Phosphodiesterases in the central nervous system: implications in mood and cognitive disorders. Handb Exp Pharmacol 204:447-485
96. Young JW, Powell SB, Risbrough V, Marston HM, Geyer MA (2009) Using the MATRICS to guide development of a preclinical cognitive test battery for research in schizophrenia. Pharmacol Ther 122:150-202