Voluntary running in young adult mice reduces anxiety-like behavior and increases the accumulation of bioactive lipids in the cerebral cortex

PLoS ONE

Volumn 8, Issue 12, 2013, Pages

  Santos Soto, Iván J ^a   Chorna, Nataliya ^a   Carballeira, Néstor M ^a   Vélez Bartolomei, José G ^a   Méndez Merced, Ana T ^b   Chornyy, Anatoliy P ^a   Peña De Ortiz, Sandra ^a  

^a UNIVERSITY OF PUERTO RICO   (Puerto Rico)

^b Universidad del Este   (Puerto Rico)

Author keywords

[No Author keywords available]

Indexed keywords

ARACHIDONIC ACID; CORTICOSTERONE; DOCOSAHEXAENOIC ACID; FATTY ACID; PALMITIC ACID; PHOSPHOLIPASE A2; POLYUNSATURATED FATTY ACID; SATURATED FATTY ACID;

ADULT; ADULT ANIMAL; ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANXIETY; ARTICLE; BEHAVIORAL POSTURE; BLOOD SAMPLING; BRAIN CORTEX; C57BL 6 MOUSE; CAGE; CEREBELLUM; CONTROLLED STUDY; CORTICOSTERONE BLOOD LEVEL; ELEVATED PLUS MAZE TEST; EXERCISE; EXPLORATORY BEHAVIOR; HIGH RISK BEHAVIOR; HIPPOCAMPUS; LIPID BRAIN LEVEL; LIPID STORAGE; LIPIDOMICS; LIPOGENESIS; MALE; MASS FRAGMENTOGRAPHY; MOOD; MOUSE; NONHUMAN; PHYSIOLOGICAL STRESS; PROTEIN EXPRESSION; RISK ASSESSMENT BEHAVIOR; RUNNING; SITTING; TRANQUILIZING ACTIVITY; VOLUNTARY EXERCISE; YOUNG ADULT;

ANIMALS; ANXIETY; ARACHIDONIC ACID; CEREBRAL CORTEX; DOCOSAHEXAENOIC ACIDS; HUMANS; LIPIDS; MICE; PALMITIC ACID; PHYSICAL CONDITIONING, ANIMAL;

EID: 84892601018     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0081459     Document Type: Article

References (111)

1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, et al. (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62: 593-602.
2. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62: 617-627.
3. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, et al. (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51: 8-19.
4. Tsatsoulis A, Fountoulakis S (2006) The protective role of exercise on stress system dysregulation and comorbidities. Ann N Y Acad Sci 1083: 196-213.
5. Harrison FE, Hosseini AH, McDonald MP (2009) Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res 198: 247-251.
6. Fordyce DE, Wehner JM (1993) Physical activity enhances spatial learning performance with an associated alteration in hippocampal protein kinase C activity in C57BL/6 and DBA/2 mice. Brain Res 619: 111-119.
7. Rhodes JS, van Praag H, Jeffrey S, Girard I, Mitchell GS, et al. (2003) Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running. Behav Neurosci 117: 1006-1016.
8. van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 96: 13427-13431.
9. van Praag H, Shubert T, Zhao C, Gage FH (2005) Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 25: 8680-8685.
10. Vaynman S, Ying Z, Gomez-Pinilla F (2004) Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci 20: 2580-2590.
11. Baruch DE, Swain RA, Helmstetter FJ (2004) Effects of exercise on Pavlovian fear conditioning. Behav Neurosci 118: 1123-1107.
12. Falls WA, Fox JH, MacAulay CM (2009) Voluntary exercise improves both learning and consolidation of cued conditioned fear in C57 mice. Behav Brain Res 207: 321-331.
13. Greenwood BN, Strong PV, Foley TE, Fleshner M (2009) A behavioral analysis of the impact of voluntary physical activity on hippocampus-dependent contextual conditioning. Hippocampus 19: 988-1001.
14. Gordon JA, Hen R (2004) Genetic approaches to the study of anxiety. Annu Rev Neurosci 27: 193-222.
15. Rodgers RJ, Dalvi A (1997) Anxiety, defense and the elevated plus-maze. Neurosci Biobehav Rev 21: 801-810.
16. Duman CH, Schlesinger L, Russell DS, Duman RS (2008) Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Res 1199: 148-158.
17. Leasure JL, Jones M (2008) Forced and voluntary exercise differentially affect brain and behavior. Neuroscience 156: 456-465.
18. Salam JN, Fox JH, Detroy EM, Guignon MH, Wohl DF, et al. (2009) Voluntary exercise in C57 mice is anxiolytic across several measures of anxiety. Behav Brain Res 197: 31-40.
19. Fuss J, Gass P (2010) Endocannabinoids and voluntary activity in mice: runner's high and long-term consequences in emotional behaviors. Exp Neurol 224: 103-105.
20. Garcia-Capdevila S, Portell-Cortes I, Torras-Garcia M, Coll-Andreu M, Costa-Miserachs D (2009) Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise. Behav Brain Res 202: 162-170.
21. Chytrova G, Ying Z, Gomez-Pinilla F (2009) Exercise contributes to the effects of DHA dietary supplementation by acting on membrane-related synaptic systems. Brain Res 1341: 32-40.
22. Wu A, Ying Z, Gomez-Pinilla F (2008) Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 155: 751-759.
23. Jump DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277: 8755-8758.
24. Kidd PM (2007) Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev 12: 207-227.
25. Marszalek JR, Lodish HF (2005) Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol 21: 633-657.
26. van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2: 266-270.
27. Kronenberg G, Bick-Sander A, Bunk E, Wolf C, Ehninger D, et al. (2006) Physical exercise prevents age-related decline in precursor cell activity in the mouse dentate gyrus. Neurobiol Aging 27: 1505-1513.
28. Olson AK, Eadie BD, Ernst C, Christie BR (2006) Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 16: 250-260.
29. Adlard PA, Perreau VM, Cotman CW (2005) The exercise-induced expression of BDNF within the hippocampus varies across life-span. Neurobiol Aging 26: 511-520.
30. Molteni R, Ying Z, Gomez-Pinilla F (2002) Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. Eur J Neurosci 16: 1107-1116.
31. Ploughman M, Granter-Button S, Chernenko G, Tucker BA, Mearow KM, et al. (2005) Endurance exercise regimens induce differential effects on brainderived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia. Neuroscience 136: 991-1001.
32. Soya H, Nakamura T, Deocaris CC, Kimpara A, Iimura M, et al. (2007) BDNF induction with mild exercise in the rat hippocampus. Biochem Biophys Res Commun 358: 961-967.
33. Vaynman S, Ying Z, Gomez-Pinilla F (2004) Exercise induces BDNF and synapsin I to specific hippocampal subfields. J Neurosci Res 76: 356-362.
34. Vaynman S, Ying Z, Wu A, Gomez-Pinilla F (2006) Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity. Neuroscience 139: 1221-1234.
35. Vaynman SS, Ying Z, Yin D, Gomez-Pinilla F (2006) Exercise differentially regulates synaptic proteins associated to the function of BDNF. Brain Res 1070: 124-130.
36. Binder E, Droste SK, Ohl F, Reul JM (2004) Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice. Behav Brain Res 155: 197-206.
37. Baruch DE, Swain RA, Helmstetter FJ (2004) Effects of exercise on Pavlovian fear conditioning. Behav Neurosci, 118(5), 1123-1127.
38. Falls WA, Fox JH, MacAulay CM (2010) Voluntary exercise improves both learning and consolidation of cued conditioned fear in C57 mice. Behav Brain Res 207(2): 321-331.
39. Ferrari PF, Palanza P, Parmigiani S, Rodgers RJ (1998) Interindividual variability in Swiss male mice: relationship between social factors, aggression, and anxiety. Physiol Behav 63: 821-827.
40. Kwak C, Lee SH, Kaang BK (2009) Social Isolation Selectively Increases Anxiety in Mice without Affecting Depression-like Behavior. Korean J Physiol Pharmacol 13: 357-360.
41. Bartolomucci A, Palanza P, Sacerdote P, Ceresini G, Chirieleison A, et al. (2003) Individual housing induces altered immuno-endocrine responses to psychological stress in male mice. Psychoneuroendocrinology 28: 540-558.
42. Palanza P (2001) Animal models of anxiety and depression: how are females different? Neurosci Biobehav Rev 25: 219-233.
43. Fediuc S, Campbell JE, Riddell MC (2006) Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats. J Appl Physiol 100: 1867-1875.
44. Droste SK, Collins A, Lightman SL, Linthorst AC, Reul JM (2009) Distinct, time-dependent effects of voluntary exercise on circadian and ultradian rhythms and stress responses of free corticosterone in the rat hippocampus. Endocrinology 150: 4170-4179.
45. Droste SK, Gesing A, Ulbricht S, Muller MB, Linthorst AC, et al. (2003) Effects of long-term voluntary exercise on the mouse hypothalamic-pituitary- adrenocortical axis. Endocrinology 144: 3012-3023.
46. Tye KM, Prakash R, Kim SY, Fenno LE, Grosenick L, et al. (2011) Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471(7338): 358-362.
47. Wang DV, Wang F, Liu J, Zhang L, Wang Z, et al. (2011) Neurons in the Amygdala with Response-Selectivity for Anxiety in Two Ethologically Based Tests. PLoS ONE 6(4): e18739. doi:10.1371/journal.pone.0018739.
48. Pysh JJ, Weiss GM (1979) Exercise during development induces an increase in Purkinje Cell dendritic tree size. Science 206 (4415): 230-232.
49. Black JE, Isaacs KR, Anderson BJ, Alcantara AA, Greenough WT (1990) Learning causes synaptogenesis, whereas motor activity causes angiogenesis in the cerebellar cortex of adult rats. Proc Natl Acad Sci U S A, 87, 5568-5572.
50. Kleim JA, Swain RA, Armstrong KA, Napper RMA, Jones TA, et al. (1998) Selective synaptic plasticity within the cerebellar cortex following complex motor skill learning. Neurobiol Learn Mem 69: 274-289.
51. Kleim JA, Hogg TM, VandenBerg PM, Cooper NR, Bruneau R, et al. (2004) Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J Neurosci 24(3): 628-33.
52. Kleim JA, Jones TA, Schallert T (2003) Motor enrichment and the induction of plasticity before or after brain injury. Neurochemical Research 28(11): 1757-1769.
53. Kleim JA, Lussnig E, Schwarz ER, Comery TA, Greenough WT (1996) Synaptogenesis and Fos expression in the motor cortex of the adult rat after motor skill learning. J Neurosci 16(14): 4529-35.
54. Anderson BJ, Eckburg PB, Relucio KI (2002) Alterations in the thickness of motor cortical subregions after motor-skill learning and exercise. Learn & Mem 9: 1-9.
55. Adkins DAL, Boychuk J, Remple MS, Kleim JA (2006) Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord. J Appl Physiol 101: 1776-1782.
56. Stranahan AM, Kalil D, Gould E (2007) Running induces widespread structural alterations in the hippocampus and the entorhinal cortex. Hippocampus 17: 1017-1022.
57. Redilla VA, Christie BR (2006) Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus. Neuroscience 137: 1299-1307.
58. Toni N, Laplagne DA, Zhao C, Gage FH, Schinder AF (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nature Neuroscience 11 (8): 901-907.
59. Toni N, Teng EM, Bushong EA, Aimone JB, Zhao C, et al. (2007) Synapse formation on neurons born in the adult hippocampus. Nat Neurosci 10(6): 727-734.
60. van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long term potentiation in mice. Proc Natl Acad Sci U S A 96(23): 13427-13431.
61. van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2(3): 266-270.
62. Carrie I, Guesnet P, Bourre JM, Frances H (2000) Diets containing long-chain n-3 polyunsaturated fatty acids affect behaviour differently during development than ageing in mice. Br J Nutr 83: 439-447.
63. Carrie I, Smirnova M, Clement M, De JD, Frances H, et al. (2002) Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n-3 polyunsaturated fatty acid deficient old mice. Nutr Neurosci 5: 43-52.
64. Moriguchi T, Greiner RS, Salem N Jr (2000) Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem 75: 2563-2573.
65. Moriguchi T, Salem N Jr (2003) Recovery of brain docosahexaenoate leads to recovery of spatial task performance. J Neurochem 87: 297-309.
66. Tanabe Y, Hashimoto M, Sugioka K, Maruyama M, Fujii Y, et al. (2004) Improvement of spatial cognition with dietary docosahexaenoic acid is associated with an increase in Fos expression in rat CA1 hippocampus. Clin Exp Pharmacol Physiol 31: 700-703.
67. Fedorova I, Hussein N, Di Martino C, Moriguchi T, Hoshiba J, et al. (2007) An n-3 fatty acid deficient diet affects mouse spatial learning in the Barnes circular maze. Prostaglandins Leukot Essent Fatty Acids 77: 269-277.
68. Greiner RS, Moriguchi T, Hutton A, Slotnick BM, Salem N Jr (1999) Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks. Lipids 34 Suppl: S239-S243.
69. Greiner RS, Moriguchi T, Slotnick BM, Hutton A, Salem N (2001) Olfactory discrimination deficits in n-3 fatty acid-deficient rats. Physiol Behav 72: 379-385.
70. Carrie I, Clement M, de Javel D, Frances H, Bourre JM (2000) Phospholipid supplementation reverses behavioral and biochemical alterations induced by n-3 polyunsaturated fatty acid deficiency in mice. J Lipid Res 41: 473-480.
71. Takeuchi T, Iwanaga M, Harada E (2003). Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Res 964: 136-143.
72. Logan AC (2004) Omega-3 fatty acids and major depression: a primer for the mental health professional. Lipids Health Dis 3: 25.
73. Ross B, Seguin J, Sieswerda L (2007) Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis 6: 21.
74. Sinclair AJ, Begg D, Mathai M, Weisinger RS (2007) Omega 3 fatty acids and the brain: review of studies in depression. Asia Pac J Clin Nutr 16 Suppl 1: 391-397.
75. Williams JH, Bliss TV (1989) An in vitro study of the effect of lipoxygenase and cyclo-oxygenase inhibitors of arachidonic acid on the induction and maintenance of long-term potentiation in the hippocampus. Neurosci Lett 107: 301-306.
76. Wolf MJ, Izumi Y, Zorumski CF, Gross RW (1995) Long-term potentiation requires activation of calcium-independent phospholipase A2. FEBS Lett 377: 358-362.
77. Pellerin L, Wolfe LS (1991) Release of arachidonic acid by NMDA-receptor activation in the rat hippocampus. Neurochem Res 16: 983-989.
78. Luo Y, Vallano ML (1995) Arachidonic acid, but not sodium nitroprusside, stimulates presynaptic protein kinase C and phosphorylation of GAP-43 in rat hippocampal slices and synaptosomes. J Neurochem 64: 1808-1818.
79. Schaechter JD, Benowitz LI (1993) Activation of protein kinase C by arachidonic acid selectively enhances the phosphorylation of GAP-43 in nerve terminal membranes. J Neurosci 13: 4361-4371.
80. Okaichi Y, Ishikura Y, Akimoto K, Kawashima H, Toyoda-Ono Y, et al. (2005) Arachidonic acid improves aged rats' spatial cognition. Physiol Behav 84: 617-623.
81. Cadas H, di Tomaso E, Piomelli D (1997) Occurrence and biosynthesis of endogenous cannabinoid precursor, N-arachidonoyl phosphatidylethanolamine, in rat brain. J Neurosci 17: 1226-1242.
82. De Oliveira Alvares L, Genro BP, Diehl F, Quillfeldt JA (2008) Differential role of the hippocampal endocannabinoid system in the memory consolidation and retrieval mechanisms. Neurobiol Learn Mem 90: 1-9.
83. Scherma M, Medalie J, Fratta W, Vadivel SK, Makriyannis A, et al. (2008) The endogenous cannabinoid anandamide has effects on motivation and anxiety that are revealed by fatty acid amide hydrolase (FAAH) inhibition. Neuropharmacology 54: 129-140.
84. Dietrich A, McDaniel WF (2004) Endocannabinoids and exercise. Br J Sports Med 38: 536-541.
85. Heyman E, Gamelin FX, Goekint M, Piscitelli F, Roelands B, et al. (2011) Intense exercise increases circulating endocannabinoid and BDNF levels in humans-possible implications for reward and depression. Psychoneuroendocrinology 37: 844-851.
86. Feuerecker M, Hauer D, Toth R, Demetz F, Holzl J, et al. (2011) Effects of exercise stress on the endocannabinoid system in humans under field conditions. Eur J Appl Physiol 112: 2777-2781.
87. Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A (2003) Exercise activates the endocannabinoid system. Neuroreport 14: 2209-2211.
88. Salaun C, Greaves J, Chamberlain LH (2010) The intracellular dynamic of protein palmitoylation. J Cell Biol 191: 1229-1238.
89. Aicart-Ramos C, Valero RA, Rodriguez-Crespo I (2011) Protein palmitoylation and subcellular trafficking. Biochim Biophys Acta 1808: 2981-2994.
90. Iwanaga T, Tsutsumi R, Noritake J, Fukata Y, Fukata M (2009) Dynamic protein palmitoylation in cellular signaling. Prog Lipid Res 48: 117-127.
91. El-Husseini Ael D, Schnell E, Dakoji S, Sweeney N, Zhou Q, et al. (2002) Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108: 849-863.
92. Hayashi T, Rumbaugh G, Huganir RL (2005) Differential regulation of AMPA receptor subunit trafficking by palmitoylation of two distinct sites. Neuron 47: 709-723.
93. Hayashi T, Thomas GM, Huganir RL (2009) Dual palmitoylation of NR2 subunits regulates NMDA receptor trafficking. Neuron 64: 213-226.
94. LoVerme J, La Rana G, Russo R, Calignano A, Piomelli D (2005) The search for the palmitoylethanolamide receptor. Life Sci 77: 1685-1698.
95. Facci L, Dal Toso R, Romanello S, Buriani A, Skaper SD, et al. (1995) Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc Natl Acad Sci U S A 92: 3376-3380.
96. Koch M, Kreutz S, Bottger C, Benz A, Maronde E, et al. (2010) Palmitoylethanolamide protects dentate gyrus granule cells via peroxisome proliferator-activated receptor-alpha. Neurotox Res 19: 330-340.
97. Matias I, Gonthier MP, Petrosino S, Docimo L, Capasso R, et al. (2007) Role and regulation of acylethanolamides in energy balance: focus on adipocytes and beta-cells. Br J Pharmacol 152: 676-690.
98. Pistis M, Melis M (2010) From surface to nuclear receptors: the endocannabinoid family extends its assets. Curr Med Chem 17: 1450-1467.
99. Raso GM, Esposito E, Vitiello S, Iacono A, Santoro A, et al. (2011) Palmitoylethanolamide stimulation induces allopregnanolone synthesis in C6 Cells and primary astrocytes: involvement of peroxisome-proliferator activated receptor-alpha. J Neuroendocrinol 23: 591-600.
100. Moise AM, Eisenstein SA, Astarita G, Piomelli D, Hohmann AG (2008) An endocannabinoid signaling system modulates anxiety-like behavior in male Syrian hamsters. Psychopharmacology (Berl) 200: 333-346.
101. Yu HL, Deng XQ, Li YJ, Li YC, Quan ZS, et al. (2011) N- palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice. Pharmacol Rep 63: 834-839.
102. Dennis EA (1994) Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem 269: 13057-13060.
103. Farooqui AA, Horrocks LA (2001) Plasmalogens: workhorse lipids of membranes in normal and injured neurons and glia. Neuroscientist 7: 232-245.
104. Clark MA, Conway TM, Shorr RG, Crooke ST (1987) Identification and isolation of a mammalian protein which is antigenically and functionally related to the phospholipase A2 stimulatory peptide melittin. J Biol Chem 262: 4402-4406.
105. Rodgers RJ, Cole JC (1993) Anxiety enhancement in the murine elevated plus maze by immediate prior exposure to social stressors. Physiol Behav 53: 383-388.
106. Perez-Acevedo NL, Lathroum L, Jorge JC (2006) The neurosteroid 3alphaDIOL modulates place preference when infused in the basolateral amygdala according to sex. Behav Neurosci 120: 632-640.
107. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911-917.
108. Xia J, Psychogios N, Young N, Wishart DS (2009) MetaboAnalyst: a web server for metabolomic data analysis and interpretation. Nucleic Acids Res 37: W652-W660.
109. Colon-Cesario WI, Martinez-Montemayor MM, Morales S, Felix J, Cruz J, et al. (2006) Knockdown of Nurr1 in the rat hippocampus: implications to spatial discrimination learning and memory. Learn Mem 13: 734-744.
110. Ren K, Pena de Ortiz S (2002) Non-homologous DNA end joining in the mature rat brain. J Neurochem 80: 949-959.
111. Wang J, Ren K, Perez J, Silva AJ, Pena de Ortiz S (2003) The antimetabolite ara-CTP blocks long-term memory of conditioned taste aversion. Learn Mem 10: 503-509.