Deficits in emotional learning and memory in an animal model of schizophrenia

Behavioural Brain Research

Volumn 233, Issue 1, 2012, Pages 35-44

  Bolton, Monica M ^a   Heaney, Chelcie F ^a   Sabbagh, Jonathan J ^a   Murtishaw, Andrew S ^a   Magcalas, Christy M ^a   Kinney, Jefferson W ^a  

^a UNIVERSITY OF NEVADA   (United States)

Author keywords

Animal models; NMDA antagonists; Pavlovian learning; Schizophrenia

Indexed keywords

4 AMINOBUTYRIC ACID A ALPHA5 RECEPTOR; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID B RECEPTOR; 4 AMINOBUTYRIC ACID B1A RECEPTOR; 4 AMINOBUTYRIC ACID B1B RECEPTOR; 4 AMINOBUTYRIC ACID B2 RECEPTOR; KETAMINE; UNCLASSIFIED DRUG;

ACOUSTIC REFLEX; AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASSOCIATION; BRAIN LEVEL; BRAIN REGION; BRAIN TISSUE; CONDITIONING; CONTEXTUAL FEAR CONDITIONING; CONTROLLED STUDY; EMOTIONAL LEARNING DISORDER; FEAR; GABAERGIC SYSTEM; HIPPOCAMPUS; LEARNING; LEARNING DISORDER; MALE; MEMORY DISORDER; NERVE CELL NETWORK; NONHUMAN; PAVLOVIAN EMOTIONAL LEARNING; PREPULSE INHIBITION; PRIORITY JOURNAL; RAT; SCHIZOPHRENIA; SENSORY GATING; SIGNAL TRANSDUCTION; STARTLE REFLEX; TAIL FLICK TEST; TASK PERFORMANCE;

ANALYSIS OF VARIANCE; ANIMALS; BRAIN; CONDITIONING, CLASSICAL; DISEASE MODELS, ANIMAL; EXCITATORY AMINO ACID ANTAGONISTS; FEAR; HINDLIMB SUSPENSION; KETAMINE; LEARNING DISORDERS; MALE; MEMORY DISORDERS; PHENCYCLIDINE; RATS; RATS, SPRAGUE-DAWLEY; REACTION TIME; RECEPTORS, GABA-B; SCHIZOPHRENIA; SENSORY GATING;

EID: 84861553889     PISSN: 01664328     EISSN: 18727549     Source Type: Journal    
DOI: 10.1016/j.bbr.2012.04.049     Document Type: Article

References (106)

1. Braff D.L., Geyer M.A. Sensorimotor gating and schizophrenia Human and animal model studies. Archives of General Psychiatry 1990, 47:181-188.
2. Kay S.R., Fiszbein A., Opler L.A. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 1987, 13:261-276.
3. Lewis D.A., Lieberman J.A. Catching up on schizophrenia: natural history and neurobiology. Neuron 2000, 28:325-334.
4. Carter C., Robertson L., Nordahl T., Chaderjian M., Kraft L., O'Shora-Celaya L. Spatial working memory deficits and their relationship to negative symptoms in unmedicated schizophrenia patients. Biological Psychiatry 1996, 40:930-932.
5. Rushe T.M., Woodruff P.W., Murray R.M., Morris R.G. Episodic memory and learning in patients with chronic schizophrenia. Schizophrenia Research 1999, 35:85-96.
6. Nuechterlein K.H., Barch D.M., Gold J.M., Goldberg T.E., Green M.F., Heaton R.K. Identification of separable cognitive factors in schizophrenia. Schizophrenia Research 2004, 72:29-39.
7. Neill J.C., Barnes S., Cook S., Grayson B., Idris N.F., McLean S.L., et al. Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacology & Therapeutics 2010, 128:419-432.
8. Keeler J.F., Robbins T.W. Translating cognition from animals to humans. Biochemical Pharmacology 2011, 81:1356-1366.
9. Benes F.M., Berretta S. GABAergic interneurons: implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 2001, 25:1-27.
10. Uhlhaas P.J., Haenschel C., Nikolic D., Singer W. The role of oscillations and synchrony in cortical networks and their putative relevance for the pathophysiology of schizophrenia. Schizophrenia Bulletin 2008, 34:927-943.
11. Cobb S.R., Buhl E.H., Halasy K., Paulsen O., Somogyi P. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 1995, 378:75-78.
12. Breese C.R., Freedman R., Leonard S.S. Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers. Brain Research 1995, 674:82-90.
13. Asada H., Kawamura Y., Maruyama K., Kume H., Ding R., Ji F.Y., et al. Mice lacking the 65kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures. Biochemical and Biophysical Research Communications 1996, 229:891-895.
14. Fatemi S.H., Hossein Fatemi S., Stary J.M., Earle J.A., Araghi-Niknam M., Eagan E. GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67kDa and Reelin proteins in cerebellum. Schizophrenia Research 2005, 72:109-122.
15. Hashimoto T., Volk D.W., Eggan S.M., Mirnics K., Pierri J.N., Sun Z., et al. Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. Journal of Neuroscience 2003, 23:6315-6326.
16. Kinney J.W., Davis C.N., Tabarean I., Conti B., Bartfai T., Behrens M.M. A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. Journal of Neuroscience 2006, 26:1604-1615.
17. Lewis D.A., Hashimoto T., Volk D.W. Cortical inhibitory neurons and schizophrenia. Nature Reviews Neuroscience 2005, 6:312-324.
18. Mirnics K., Middleton F., Marquez A.A., Lewis D.A., Levitt P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 2000, 28:53-67.
19. Reynolds G.P., Zhang Z.J., Beasley C.L. Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity. Brain Research Bulletin 2001, 55:579-584.
20. Torrey E.F., Barci B.M., Webster M.J., Bartko J., Meador-Woodruff J.H., Knable M.B. Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biological Psychiatry 2005, 57:252-260.
21. Adler C.M., Malhotra A.K., Elman I., Goldberg T., Egan M., Pickar D., et al. Comparison of ketamine-induced thought disorder in healthy volunteers and thought disorder in schizophrenia. American Journal of Psychiatry 1999, 156:1646-1649.
22. Krystal J.H., Karper L.P., Seibyl J.P., Freeman G.K., Delaney R., Bremner J.D., et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Archives of General Psychiatry 1994, 51:199-214.
23. Malhotra A.K., Pinals D.A., Weingartner H., Sirocco K., Missar C.D., Pickar D., et al. NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 1996, 14:301-307.
24. Luby E.D., Cohen B.D., Rosenbaum G., Gottlieb J.S., Kelley R. Study of a new schizophrenomimetic drug-sernyl. A.M.A. Archives of Neurology and Psychiatry 1959, 81:363-369.
25. Luby E.D., Gottlieb J.S., Cohen B.D., Rosenbaum G., Domino E.F. Model psychoses and schizophrenia. American Journal of Psychiatry 1962, 119:61-67.
26. Lahti A.C., Holcomb H.H., Medoff D.R., Tamminga C.A. Ketamine activates psychosis and alters limbic blood flow in schizophrenia. Neuroreport 1995, 6:869-872.
27. Lahti A.C., Koffel B., LaPorte D., Tamminga C.A. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology 1995, 13:9-19.
28. Geyer M.A., Swerdlow N.R., Mansbach R.S., Braff D.L. Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Research Bulletin 1990, 25:485-498.
29. Javitt D.C., Zukin S.R. Recent advances in the phencyclidine model of schizophrenia. American Journal of Psychiatry 1991, 148:1301-1308.
30. Ogawa S., Okuyama S., Araki H., Nakazato A., Otomo S. A rat model of phencyclidine psychosis. Life Sciences 1994, 55:1605-1610.
31. Steinpreis R.E. The behavioral and neurochemical effects of phencyclidine in humans and animals: some implications for modeling psychosis. Behavioural Brain Research 1996, 74:45-55.
32. Becker A., Peters B., Schroeder H., Mann T., Huether G., Grecksch G. Ketamine-induced changes in rat behaviour: a possible animal model of schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2003, 27:687-700.
33. Bickel S., Javitt D.C. Neurophysiological and neurochemical animal models of schizophrenia: focus on glutamateâñ†. Behavioural Brain Research 2009, 204:352-362.
34. Li Q., Clark S., Lewis D.V., Wilson W.A. NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: a potential mechanism of neurotoxicity. Journal of Neuroscience 2002, 22:3070-3080.
35. McGaugh J.L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience 2004, 27:1-28.
36. Phelps E.A. Human emotion and memory: interactions of the amygdala and hippocampal complex. Current Opinion in Neurobiology 2004, 14:198-202.
37. Hall J., Harris J.M., McKirdy J.W., Johnstone E.C., Lawrie S.M. Emotional memory in schizophrenia. Neuropsychologia 2007, 45:1152-1159.
38. Hamann S.B., Ely T.D., Grafton S.T., Kilts C.D. Amygdala activity related to enhanced memory for pleasant and aversive stimuli. Nature Neuroscience 1999, 2:289-293.
39. Canli T., Zhao Z., Brewer J., Gabrieli J.D., Cahill L. Event-related activation in the human amygdala associates with later memory for individual emotional experience. Journal of Neuroscience 2000, 20:RC99.
40. Gur R.E., McGrath C., Chan R.M., Schroeder L., Turner T., Turetsky B.I., et al. An fMRI study of facial emotion processing in patients with schizophrenia. American Journal of Psychiatry 2002, 159:1992-1999.
41. Herbener E.S., Rosen C., Khine T., Sweeney J.A. Failure of positive but not negative emotional valence to enhance memory in schizophrenia. Journal of Abnormal Psychology 2007, 116:43-55.
42. Kring A.M., Caponigro J.M. Emotion in schizophrenia: where feeling meets thinking. Current Directions in Psychological Science 2010, 19:255-259.
43. Aleman A., Kahn R. Strange feelings: do amygdala abnormalities dysregulate the emotional brain in schizophrenia. Progress in Neurobiology 2005, 77:283-298.
44. Das P., Kemp A.H., Flynn G., Harris A.W.F., Liddell B.J., Whitford T.J., et al. Functional disconnections in the direct and indirect amygdala pathways for fear processing in schizophrenia. Schizophrenia Research 2007, 90:284-294.
45. Kosaka H., Omori M., Murata T., Iidaka T., Yamada H., Okada T., et al. Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study. Schizophrenia Research 2002, 57:87-95.
46. Whalley H.C., McKirdy J., Romaniuk L., Sussmann J., Johnstone E., Wan H.I., et al. Functional imaging of emotional memory in bipolar disorder and schizophrenia. Bipolar Disorders 2009, 11:840-856.
47. Dolcos F., LaBar K.S., Cabeza R. Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related fMRI study. Neuroimage 2004, 23:64-74.
48. Schneider F., Weiss U., Kessler C., Salloum J.B., Posse S., Grodd W., et al. Differential amygdala activation in schizophrenia during sadness. Schizophrenia Research 1998, 34:133-142.
49. Achim M., Lepage M. Episodic memory-related activation in schizophrenia: meta-analysis. British Journal of Psychiatry 2005, 187:500-509.
50. Phillips R.G., LeDoux J.E. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behavioral Neuroscience 1992, 106:274-285.
51. Kinney J.W., Starosta G., Holmes A., Wrenn C.C., Yang R.J., Harris A.P., et al. Deficits in trace cued fear conditioning in galanin-treated rats and galanin-overexpressing transgenic mice. Learning and Memory 2002, 9:178-190.
52. Gao C., Gill M.B., Tronson N.C., Guedea A.L., Guzman Y.F., Huh K.H., et al. Hippocampal NMDA receptor subunits differentially regulate fear memory formation and neuronal signal propagation. Hippocampus 2010, 20:1072-1082.
53. Maren S., Quirk G.J. Neuronal signalling of fear memory. Nature Reviews Neuroscience 2004, 5:844-852.
54. LeDoux J.E. Emotion circuits in the brain. Annual Review of Neuroscience 2000, 23:155-184.
55. Lee H., Kim J.J. Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats. Journal of Neuroscience 1998, 18:8444-8454.
56. Li X.F., Phillips R.G., LeDoux J.E. NMDA and non-NMDA receptors contribute to synaptic transmission between the medial geniculate body and the lateral nucleus of the amygdala. Experimental Brain Research 1995, 105:87-100.
57. LeDoux J.E., Cicchetti P., Xagoraris A., Romanski L.M. The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning. Journal of Neuroscience 1990, 10:1062-1069.
58. Davis M., Whalen P.J. The amygdala: vigilance and emotion. Molecular Psychiatry 2001, 6:13-34.
59. Schafe G.E., Nader K., Blair H.T., LeDoux J.E. Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective. Trends in Neurosciences 2001, 24:540-546.
60. LeDoux J. The emotional brain, fear, and the amygdala. Cellular and Molecular Neurobiology 2003, 23:727-738.
61. Chen C., Kim J.J., Thompson R.F., Tonegawa S. Hippocampal lesions impair contextual fear conditioning in two strains of mice. Behavioral Neuroscience 1996, 110:1177-1180.
62. Logue S.F., Paylor R., Wehner J.M. Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task. Behavioral Neuroscience 1997, 111:104-113.
63. Holland P.C., Bouton M.E. Hippocampus and context in classical conditioning. Current Opinion in Neurobiology 1999, 9:195-202.
64. Beylin A.V., Gandhi C.C., Wood G.E., Talk A.C., Matzel L.D., Shors T.J. The role of the hippocampus in trace conditioning: temporal discontinuity or task difficulty. Neurobiology of Learning and Memory 2001, 76:447-461.
65. Solomon P.R., Vander Schaaf E.R., Thompson R.F., Weisz D.J. Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response. Behavioral Neuroscience 1986, 100:729-744.
66. Moyer J.R.J., Deyo R.A., Disterhoft J.F. Hippocampectomy disrupts trace eye-blink conditioning in rabbits. Behavioral Neuroscience 1990, 104:243-252.
67. Sutherland R.J., McDonald R.J. Hippocampus amygdala, and memory deficits in rats. Behavioural Brain Research 1990, 37:57-79.
68. McEchron M.D., Bouwmeester H., Tseng W., Weiss C., Disterhoft J.F. Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat. Hippocampus 1998, 8:638-646.
69. McEchron M.D., Tseng W., Disterhoft J.F. Neurotoxic lesions of the dorsal hippocampus disrupt auditory-cued trace heart rate (fear) conditioning in rabbits. Hippocampus 2000, 10:739-751.
70. Weiss C., Bouwmeester H., Power J.M., Disterhoft J.F. Hippocampal lesions prevent trace eyeblink conditioning in the freely moving rat. Behavioural Brain Research 1999, 99:123-132.
71. Ryou J.W., Cho S.Y., Kim H.T. Lesions of the entorhinal cortex impair acquisition of hippocampal-dependent trace conditioning. Neurobiology of Learning and Memory 2001, 75:121-127.
72. Johansson C., Jackson D.M., Zhang J., Svensson L. Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: effects of antipsychotics and other agents in rats. Pharmacology Biochemistry & Behavior 1995, 52:649-654.
73. Cilia J., Hatcher P., Reavill C., Jones D.N.C. (±) Ketamine-induced prepulse inhibition deficits of an acoustic startle response in rats are not reversed by antipsychotics. Journal of Psychopharmacology (Oxford) 2007, 21:302-311.
74. Olney J.W., Labruyere J., Wang G., Wozniak D.F., Price M.T., Sesma M.A. NMDA antagonist neurotoxicity: mechanism and prevention. Science 1991, 254:1515-1518.
75. Rujescu D., Bender A., Keck M., Hartmann A.M., Ohl F., Raeder H., et al. A pharmacological model for psychosis based on n-methyl-d-aspartate receptor hypofunction: molecular, cellular, functional and behavioral abnormalities. Biological Psychiatry 2006, 59:721-729.
76. Gunduz-Bruce H. The acute effects of NMDA antagonism: from the rodent to the human brain. Brain Research Reviews 2009, 60:279-286.
77. Keilhoff G., Becker A., Grecksch G., Wolf G., Bernstein H.G. Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthanse and cFos similar to those found in human schizophrenia. Neuroscience 2004, 126:591-598.
78. Zhang Y.P., Behrens M.M., Lisman J.E. Prolonged exposure to NMDAR antagonist supresses inhibitory synaptic transmission in prefrontal cortex. Journal of Neurophysiology 2008, 100:959-965.
79. Sabbagh JJ, Heaney CF, Bolton MM, Murtishaw AS, Kinney JW. Efficacy of acute versus chronic administration of an NMDA receptor antagonist to induce an animal model of schizophrenia. Unpublished results.
80. Huerta P.T., Sun L.D., Wilson M.A. Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons. Neuron 2000, 25:473-480.
81. Andre J.M., Leach P.T., Gould T.J. Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus. Neuropharmacology 2011, 60:617-625.
82. Chess A.C., Landers A.M., Bucci D.J. l-kynurenine treatment alters contextual fear conditioning and context discrimination but not cue-specific fear conditioning. Behavioural Brain Research 2009, 201:325-331.
83. Bardgett M.E., Boeckman R., Krochmal D., Fernando H., Ahrens R., Csernansky J.G. NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice. Brain Research Bulletin 2003, 60:131-142.
84. Tan S., Kirk R.C., Abraham W.C., McNaughton N Effects of the NMDA antagonists CPP and MK-801 on delayed conditional discrimination. Psychopharmacology (Berl) 1989, 98:556-560.
85. Kim J., Fanselow M. Modality-specific retrograde amnesia of fear. Science 1992, 256:675-677.
86. Paylor R., Nguyen M., Crawley J.N., Patrick J., Beaudet A., Orr-Urtreger A. a7 Nicotinic receptor subunits are not necessary for hippocampal-dependent learning or sensorimotor gating: a behavioral characterization of acra7-deficient mice. Learning and Memory 1998, 5:302-316.
87. Phillips R.G., LeDoux J.E. Lesions of the dorsal hippocampal formation interfere with background but not foreground contextual fear conditioning. Learning and Memory 1994, 1:34-44.
88. Maren S., Aharonov G., Faneslow M.S. Retrograde abolition of conditional fear after excitotoxic lesions in the basolateral amygdala of rats: absence of a temporal gradient. Behavioral Neuroscience 1996, 110:718-726.
89. McNish K.A., Gewirtz J.C., Davis M. Evidence of contextual fear after lesions of the hippocampus: a disruption of freezing but not fear-potentiated startle. Journal of Neuroscience 1997, 17:9353-9360.
90. Anagnostaras S.G., Maren S., Faneslow M.S. Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination. Journal of Neuroscience 1999, 19:1106-1114.
91. Antoniadis E.A., McDonald R.J. Amygdala, hippocampus and discriminative fear conditioning to context. Behavioural Brain Research 2000, 109:141-142.
92. Gewirtz J.C., McNish K.A., Davis M. Is the hippocampus necessary for contextual fear conditioning. Behavioural Brain Research 2000, 110:83-95.
93. Swerdlow N.R., Weber M., Qu Y. Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology 2008, 199:331-388.
94. Swerdlow N.R., Braff D.L., Taaid N., Geyer M.A. Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Archives of General Psychiatry 1994, 51:139-154.
95. Swerdlow N.R., Geyer M.A., Braff D.L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 2001, 156:194-215.
96. Kohl M.M., Paulsen O. The roles of GABAB receptors in cortical network activity. Advances in Pharmacology 2010, 58:205-229.
97. Gonzalez-Burgos G. GABA transporter GAT1: a crucial determinant of GABAB receptor activation in cortical circuits. Advances in Pharmacology 2010, 58:175-204.
98. 2+ spikes in layer 5 somatosensory pyramidal neurons. Neuron 2006, 50:603-616.
99. Bowery N.G., Bettler B., Froestl W., Gallagher J.P., Marshall F., Raiteri M., et al. International Union of Pharmacology XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: structure and function. Pharmacological Reviews 2002, 54:247-264.
100. Marshall F.H., Jones K.A., Kaupmann K., Bettler B. GABAB receptors - the first 7TM heterodimers. Trends in Pharmacological Sciences 1999, 20:396-399.
101. Vigot R., Barbieri S., Brauner-Osborne H., Turecek R., Shigemoto R., Zhang Y.P., et al. Differential compartmentalization and distinct functions of GABAB receptor variants. Neuron 2006, 50:589-601.
102. Ulrich D., Bettler B. GABA(B) receptors: synaptic functions and mechanisms of diversity. Current Opinion in Neurobiology 2007, 17:298-303.
103. Ladera C., del Carmen Godino M., Jose Cabanero M., Torres M., Watanabe M., Lujan R., et al. Pre-synaptic GABA receptors inhibit glutamate release through GIRK channels in rat cerebral cortex. Journal of Neurochemistry 2008, 107:1506-1517.
104. Hauser J., Rudolph U., Keist R., Mohler H., Feldon J., Yee B.K. Hippocampal a5 subunit-containing GABAA receptors modulate the expression of prepulse inhibition. Molecular Psychiatry 2005, 10:201-207.
105. Pietersen C.Y., Bosker F.J., Doorduin J., Jongsma M.E., Postema F., Haas J.V., Johnson M.P., Koch T., Vladusich T., den Boer JA An animal model of emotional blunting in schizophrenia. PLoS ONE 2007, 2(12):e1360.
106. Amann L.C., Halenel T.B., Ehrlichman R.S., Luminasi S.N., Ma N., Abel T., Siegel S.J. Chronic ketamine impairs fear conditioning and produces long lasting reductions in auditory evoked potentials. Neurobiology of Disease 2009, 35(2):311-317.