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Environmental enrichment, prefrontal cortex, stress, and aging of the brain

  • Basic Neurosciences, Genetics and Immunology - Review Article
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Abstract

As a result of living in an enriched environment, the brain of animals undergoes molecular and morphological changes leading to improvements in learning and memory. These improvements correlate well with increase in neurogenesis, synaptic density, or neurotrophic factors. We review here, in the context of the literature, the experiments performed in our own laboratory on the effects of environmental enrichment on the dynamics of dopamine and acetylcholine in the prefrontal cortex under a situation of acute mild stress. In these last studies we found that the release of dopamine and acetylcholine under stress is reduced in animals housed in an enriched environment. We also reported that the stress-induced release of dopamine but not acetylcholine is lower in aged rats compared with young rats. These results suggest that environmental enrichment reduces the reactivity to stress of the prefrontal dopaminergic and cholinergic systems in the rat. We further hypothesize that the positive effects on stress coping behaviors of housing animals in an enriched environment are associated with reductions, rather than increases, in the release of dopamine and acetylcholine in the prefrontal cortex. Finally we propose that a reduction in the stress-induced release of dopamine observed during aging in control animals might be an index of a better adaptation to stressful stimuli.

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References

  • Abercrombie ED, Keefe KA, Daniel SD, Zigmond MJ (1989) Differential effects of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex. J Neurochem 52:1655–1658

    PubMed  CAS  Google Scholar 

  • Acquas E, Wilson C, Fibiger HC (1996) Conditioned and unconditioned stimuli increase frontal cortical and hippocampal acetylcholine release: effects of novelty, habituation, and fear. J Neurosci 16:3089–3096

    PubMed  CAS  Google Scholar 

  • Aggleton JP, Blindt HS, Candy JM (1989) Working memory in aged rats. Behav Neurosci 103:975–983

    PubMed  CAS  Google Scholar 

  • Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF (2005) Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus. Nat Neurosci 8:365–371

    PubMed  CAS  Google Scholar 

  • Amat J, Paul E, Zarza C, Watkins LR, Maier SF (2006) Previous experience with behavioral control over stress blocks the behavioral and dorsal raphe nucleus activating effects of later uncontrollable stress: role of the ventral medial prefrontal cortex. J Neurosci 26:13264–13272

    PubMed  CAS  Google Scholar 

  • Arnsten AFT (1998) Neuroscience: enhanced: the biology of being frazzled. Science 280:1711–1712

    PubMed  CAS  Google Scholar 

  • Arnsten AF, Goldman-Rakic PS (1998) Noise stress impairs prefrontal cortical cognitive function in monkeys. Arch Gen Psychiatry 55:362–368

    PubMed  CAS  Google Scholar 

  • Bardo MT, Bowling SL, Rowlett JK, Manderscheid P, Buxton ST, Dwoskin LP (1995) Environmental enrichment attenuates locomotor sensitization, but not in vitro dopamine release, induced by amphetamine. Pharmacol Biochem Behav 51:397–405

    PubMed  CAS  Google Scholar 

  • Baskerville KA, Kent C, Nicolle MM, Gallagher M, McKinney M (2006) Aging causes partial loss of basal forebrain but no loss of pontine reticular cholinergic neurons. Neuroreport 17:1819–1823

    PubMed  CAS  Google Scholar 

  • Berretta S, Pantazopoulos H, Caldera M, Pantazopoulos P, Paré D (2005) Infralimbic cortex activation increases c-fos expression in intercalated neurons of the amygdala. Neuroscience 132:943–953

    PubMed  CAS  Google Scholar 

  • Bezard E, Dovero S, Belin D, Duconger S, Jackson-Lewis V, Przedborski S, Piazza PV, Gross CE, Jaber M (2003) Enriched environment confers resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and cocaine: involvement of dopamine transporter and trophic factors. J Neurosci 23:10999–11007

    PubMed  CAS  Google Scholar 

  • Biegon A, Duvdevani R, Greenberger V, Segal M (1988) Aging and brain cholinergic muscarinic receptors: an autoradiographic study in the rat. J Neurochem 51:1381–1385

    PubMed  CAS  Google Scholar 

  • Bland ST, Hargrave D, Pepin JL, Amat J, Watkins LR, Maier SF (2003) Stressor controllability modulates stress-induced dopamine and serotonin efflux and morphine-induced serotonin efflux in the medial prefrontal cortex. Neuropsychopharmacology 28:1589–1596

    PubMed  CAS  Google Scholar 

  • Bowling SL, Rowlett JK, Bardo MT (1993) The effect of enviromental enrichment on amphetamine-sitimulated locomotor activity, dopamine synthesis and dopamine release. Neuropharmacology 32:885–893

    PubMed  CAS  Google Scholar 

  • Bredy TW, Zhang TY, Grant RJ, Diorio J, Meaney MJ (2004) Peripubertal environmental enrichment reverses the effects of maternal care on hippocampal development and glutamate receptor subunit expression. Eur J Neurosci 20:1355–1362

    PubMed  Google Scholar 

  • Burke SN, Barnes CA (2006) Neural plasticity in the ageing brain. Nat Neurosci 7:30–40

    CAS  Google Scholar 

  • Cai JX, Arnsten AF (1997) Dose-dependent effects of the dopamine D1 receptor agonists A77636 or SKF81297 on spatial working memory in aged monkeys. J Pharmacol Exp Ther 283:183–189

    PubMed  CAS  Google Scholar 

  • Castner SA, Goldman-Rakic PS (2004) Enhancement of working memory in aged monkeys by a sensitizing regimen of dopamine D1 receptor stimulation. J Neurosci 24:1446–1450

    PubMed  CAS  Google Scholar 

  • Charles ST, Almeida DM (2007) Genetic and environmental effects on daily life stressors: more evidence for greater variation in later life. Psychol Aging 22:331–340

    PubMed  Google Scholar 

  • Churchill JD, Galvez R, Colcombe S, Swain RA, Kramer AF, Greenough WT (2002) Exercise, experience and the aging brain. Neurobiol Aging 23:941–955

    PubMed  Google Scholar 

  • Cobo M, Expósito I, Porras A, Mora F (1992) Release of amino acid neurotransmitters in different cortical areas of conscious adult and aged rats. Neurobiol Aging 13:705–709

    PubMed  CAS  Google Scholar 

  • Cobo M, Expósito I, Mora F (1993) Aging, prefrontal cortex, and amino acid neurotransmitters: differential effects produced by electrical stimulation. Neurobiol Aging 14:187–190

    PubMed  CAS  Google Scholar 

  • Cools R, Robbins TW (2004) Chemistry of the adaptive mind. Philos Trans R Soc Lond A 362:2871–2888

    CAS  Google Scholar 

  • Davis M, Hithcock JM, Bowers MB, Berridge CW, Melia KR, Roth RH (1994) Stress-induced activation of prefrontal cortex dopamine turnover: blockade by lesions of the amygdala. Brain Res 664:207–210

    PubMed  CAS  Google Scholar 

  • Dazzi L, Vacca G, Ladu S, Pisu MG, Serra M, Biggio G (2001) Long-term treatment with antidepressant drugs reduces the sensitivity of cortical cholinergic neurons to the activating actions of stress and the anxiogenic drug FG 7142. Neuropharmacology 41:229–237

    PubMed  CAS  Google Scholar 

  • de Kloet ER, Joëls M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475

    PubMed  Google Scholar 

  • Decker MW (1987) The effects of aging on hippocampal and cortical projections of the forebrain cholinergic system. Brain Res Rev 12:423–438

    CAS  Google Scholar 

  • Del Arco A, Mora F (2001) Dopamine release in the prefrontal cortex during stress is reduced by the local activation of glutamate receptors. Brain Res Bull 56:125–130

    PubMed  CAS  Google Scholar 

  • Del Arco A, Mora F (2005) Glutamate-dopamine in vivo interaction in the prefrontal cortex modulates the release of dopamine and acetylcholine in the nucleus accumbens of the awake rat. J Neural Transm 112:97–109

    PubMed  CAS  Google Scholar 

  • Del Arco A, Segovia G, Mora F (2001) Dopamine release during stress in the prefrontal cortex of the rat decreases with age. Neuroreport 12:4019–4022

    PubMed  CAS  Google Scholar 

  • Del Arco A, Segovia G, Canales JJ, Garrido P, De Blas M, García-Verdugo JM, Mora F (2007a) Environmental enrichment reduces the function of D1 dopamine receptors in the prefrontal cortex of the rat. J Neural Transm 114:43–48

    PubMed  CAS  Google Scholar 

  • Del Arco A, Segovia G, Garrido P, De Blas M, Mora F (2007b) Stress, prefrontal cortex and environmental enrichment: Studies on dopamine and acetylcholine release and working memory performance in rats. Behav Brain Res 176:267–273

    PubMed  CAS  Google Scholar 

  • Diamond MC (2001) Response of the brain to enrichment. An Acad Bras Cienc 73:211–218

    PubMed  CAS  Google Scholar 

  • Enrico P, Bouma M, De Vries JB, Westerink BHC (1998) The role of afferents to the ventral tegmental area in the handling stress-induced increase in the release of dopamine in the medial prefrontal cortex: a dual-probe microdialysis study in the rat brain. Brain Res 779:205–213

    PubMed  CAS  Google Scholar 

  • Faherty CJ, Shepherd KR, Herasimtschuk A, Smeyne RJ (2005) Environmental enrichment in adulthood eliminates neuronal death in experimental Parkinsonism. Brain Res Mol Brain Res 134:170–179

    PubMed  CAS  Google Scholar 

  • Feenstra MGP, Botterblom MHA, Mastenbroek S (2000) Dopamine and noradrenaline efflux in the prefrontal cortex in the light and dark period: effects of novelty and handling and comparison to the nucleus accumbens. Neuroscience 100:741–748

    PubMed  CAS  Google Scholar 

  • Fernández-Teruel A, Giménez-Llort L, Escorihuela RM, Gil L, Aguilar R, Steimer T, Tobeña A (2002) Early-life handling stimulation and environmental enrichment. Are some of their effects mediated by similar neural mechanisms? Pharmacol Biochem Behav 73:233–245

    PubMed  Google Scholar 

  • Fischer W, Wictorin K, Bjorklund A, Williams LR, Varon S, Gage FH (1987) Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329:65–68

    PubMed  CAS  Google Scholar 

  • Foster TC, Gagné J, Massicotte G (1996) Mechanism of altered synaptic strength due to experience: relation to long-term potentiation. Brain Res 736:243–250

    PubMed  CAS  Google Scholar 

  • Fox C, Merali Z, Harrison C (2006) Therapeutic and protective effect of environmental enrichment against psychogenic and neurogenic stress. Behav Brain Res 175:1–8

    PubMed  CAS  Google Scholar 

  • Frick KM, Baxter MG, Markowska AL, Olton DS, Price DL (1995) Age-related spatial reference and working memory deficits assesed in the water maze. Neurobiol Aging 16:149–160

    PubMed  CAS  Google Scholar 

  • Fuster JM (1997) The prefrontal cortex. Anatomy, physiology, and neuropsychology of the frontal lobe. Lippincott-Raven, New York

    Google Scholar 

  • Gabbott PLA, Warner TA, Jays PRL, Salway P, Busby SJ (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492:145–177

    PubMed  Google Scholar 

  • Garrido P, De Blas M, Del Arco A, Segovia G, Mora F (2008) Environmental enrichment suppresses dopamine and coricosterone increases produced by acute stress in the prefrontal cortex of the rat. FENS Abstr 4:114.8

    Google Scholar 

  • Goldman-Rakic PS, Brown RM (1981) Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 6:177–187

    PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS, Muly ECIII, Williams GV (2000) D1 receptors in prefrontal cells and circuits. Brain Res Rev 31:295–301

    PubMed  CAS  Google Scholar 

  • Goldstein LE, Rasmusson AM, Bunney BS, Roth RH (1996) Role of the amygdala in the coordination of behavioral, neuroendocrine, and prefrontal cortical monoamine responses to psychological stress in the rat. J Neurosci 16:4787–4798

    PubMed  CAS  Google Scholar 

  • Goudsmit E, Feenstra MGP, Swaab DF (1990) Central monoamine metabolism in the male brown-Norway rat in relation to aging and testosterone. Brain Res Bull 25:755–763

    PubMed  CAS  Google Scholar 

  • Hains AB, Arnsten AFT (2008) Molecular mechanisms of stress-induced prefrontal cortical impairment: Implications for mental illness. Learn Mem 15:551–564

    PubMed  Google Scholar 

  • Hedden T, Gabrieli JDE (2004) Insights into the ageing mind: a view from cognitive neuroscience. Nat Rev Neurosci 5:87–96

    PubMed  CAS  Google Scholar 

  • Kitchener P, Di Blasi F, Borrelli E, Piazza PV (2004) Differences between brain structures in nuclear translocation and DNA binding of the glucocorticoid receptor during stress and the circadian cycle. Eur J Neurosci 19:1837–1846

    PubMed  Google Scholar 

  • Kudielka BM, Buske-Kirschbaum A, Hellhammer DH, Kirschbaum C (2004) Differential heart rate reactivity and recovery after psychosocial stress (TSST) in healthy children, younger adults, and elderly adults: the impact of age and gender. Int J Behav Med 11:116–121

    PubMed  Google Scholar 

  • Laplante F, Stevenson CW, Gratton A, Srivastava LK, Quirion R (2004) Effects of neonatal ventral hippocampal lesion in rats on stress-induced acetylcholine release in the prefrontal cortex. J Neurochem 91:1473–1482

    PubMed  CAS  Google Scholar 

  • Larsson F, Winblad B, Mohammed AH (2002) Psychological stress and environmental adaptation in enriched versus impoverished housed rats. Pharmacol Biochem Behav 73:193–207

    PubMed  CAS  Google Scholar 

  • Lee JM, Ross ER, Gower A, Paris JM, Martensson R, Lorens SA (1994) Spatial learning deficits in the aged rat: neuroanatomical and neurochemical correlates. Brain Res Bull 33:489–500

    PubMed  CAS  Google Scholar 

  • Linthorst ACE, Reul JM (2008) Stress and the brain: solving the puzzle using microdialysis. Pharmacol Biochem Behav 90:163–173

    PubMed  CAS  Google Scholar 

  • Luine V, Hearns M (1990) Spatial memory deficits in aged rats: contributions of the cholinergic system assessed by ChAT. Brain Res 523:321–324

    PubMed  CAS  Google Scholar 

  • Luine V, Bowling D, Hearns M (1990) Spatial memory deficits in aged rats: contributions of monoaminergic systems. Brain Res 537:271–278

    PubMed  CAS  Google Scholar 

  • Maier SF, Amat J, Baratta MV, Paul E, Watkins LR (2006) Behavioral control, the medial prefrontal cortex, and resilience. Dialogues Clin Neurosci 8:397–406

    PubMed  Google Scholar 

  • Mark GP, Rada PV, Shors TJ (1996) Inescapable stress enhances extracellular acetylcholine in the rat hippocampus and prefrontal cortex but not the nucleus accumbens or amygdala. Neuroscience 74:767–774

    PubMed  CAS  Google Scholar 

  • Marx J (2005) Preventing Alzheimer’s: a lifelong commitment? Science 309:864–866

    PubMed  CAS  Google Scholar 

  • Maswood S, Barter JE, Watkins LR, Maier SF (1998) Exposure to inescapable but not escapable shock increases extracellular levels of 5-HT in the dorsal raphe nucleus of the rat. Brain Res 783:115–120

    PubMed  CAS  Google Scholar 

  • Mattson MP, Magnus T (2006) Ageing and neuronal vulnerability. Nat Rev Neurosci 7:278–294

    PubMed  CAS  Google Scholar 

  • McEwen BS (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87:873–904

    PubMed  Google Scholar 

  • Means LW, Kennard KJP (1991) Working memory and the aged rat: deficient two-choice win-stay water-escape acquisition and retention. Physiol Behav 49:301–307

    PubMed  CAS  Google Scholar 

  • Melendez RI, Gregory ML, Bardo MT, Kalivas PW (2004) Impoverished rearing environment alters metabotropic glutamate receptor expression and function in the prefrontal cortex. Neuropsychopharmacology 29:1980–1987

    PubMed  CAS  Google Scholar 

  • Mirmiran M, Van Gool WA, Van Haaren F, Polak CE (1986) Environmental influences on brain and behavior in aging and Alzheimer’s disease. In: Swaab DF, Fliers E, Mirmiran M, Van Gool WA, Van Haaren F (eds) Aging of the brain and alzheimer’s disease. Progress in Brain Research, vol 70. Elsevier, Amsterdam

    Google Scholar 

  • Mlynarik M, Johansson BB, Jezova D (2004) Enriched environment influences adrenocortical response to immune challenge and glutamate receptor gene expression in rat hippocampus. Ann N Y Acad Sci 1018:273–280

    PubMed  CAS  Google Scholar 

  • Mohammed AH, Zhu SW, Darmopil S, Hjerling-Leffler J, Ernfors P, Winblad B, Diamond MC, Eriksson PS, Bogdanovic N (2002) Environmental enrichment and the brain. Progress in Brain Research. Elsevier, Amsterdam

    Google Scholar 

  • Moncek F, Duncko R, Johansson BB, Jezova D (2004) Effect of environmental enrichment on stress related systems in rats. J Neuroendocrinol 16:423–431

    PubMed  CAS  Google Scholar 

  • Mora F, Sweeney KF, Rolls ET, Sanguinetti AM (1976) Spontaneous firing rate of neurons in the prefrontal cortex of the rat: evidence for a dopaminergic inhibition. Brain Res 116:516–522

    PubMed  CAS  Google Scholar 

  • Mora F, Segovia G, Del Arco A (2007) Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain. Brain Res Rev 55:78–88

    PubMed  CAS  Google Scholar 

  • Mora F, Segovia G, Del Arco A (2008) Glutamate–dopamine–GABA interactions in the aging basal ganglia. Brain Res Rev 58:340–353

    PubMed  CAS  Google Scholar 

  • Murphy BL, Arnsten AFT, Goldman-Rakic PS, Roth RH (1996) Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys. Proc Natl Acad Sci USA 93:1325–1329

    PubMed  CAS  Google Scholar 

  • Naka F, Narita N, Okado N, Narita M (2005) Modification of AMPA receptor properties following environmental enrichment. Brain Dev 27:275–278

    PubMed  Google Scholar 

  • Nithianantharajah J, Hannan AJ (2006) Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 7:697–709

    PubMed  CAS  Google Scholar 

  • Perls ET, Silver MH (2000) Living to 100: lessons in living your maximum potential at any age. Basic Books, New York

    Google Scholar 

  • Phillips AG, Ahn S, Floresco SB (2004) Magnitude of dopamine release in medial prefrontal cortex predict accuracy of memory on delayed response task. J Neurosci 24:547–553

    PubMed  CAS  Google Scholar 

  • Porras A, Sanz B, Mora F (1997) Dopamine–glutamate interactions in the prefrontal cortex of the conscious rat: studies on ageing. Mech Ageing Dev 99:9–17

    PubMed  CAS  Google Scholar 

  • Rasmuson S, Olsson T, Henriksson BG, Kelly PAT, Holmes MC, Seckl JR, Mohammed AH (1998) Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus. Mol Brain Res 53:285–290

    PubMed  CAS  Google Scholar 

  • Robbins TW (1997) Arousal systems and attentional processes. Biol Psychiatry 45:57–71

    Article  CAS  Google Scholar 

  • Robbins TW (2000) From arousal to cognition: integrative position of the prefrontal cortex. Prog Brain Res 126:469–483

    PubMed  CAS  Google Scholar 

  • Robbins TW (2005) Controlling stress: how the brain protects itself from depression. Nat Neurosci 8:261–262

    PubMed  CAS  Google Scholar 

  • Rosenkranz JA, Grace AA (2002) Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo. J Neurosci 22:324–337

    PubMed  CAS  Google Scholar 

  • Rosenzweig MR, Bennett EL (1996) Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav Brain Res 78:57–65

    PubMed  CAS  Google Scholar 

  • Rouge-Pont F, Deroche V, Le Moal M, Piazza PV (1998) Individual differences in stress-induced dopamine release in the nucleus accumbens are influenced by corticosterone. Eur J Neurosci 10:3903–3907

    PubMed  CAS  Google Scholar 

  • Sarter M, Bruno JP (2000) Cortical cholinergic inputs mediating arousal, attentional processing and dreaming: differential afferent regulation of the basal forebrain by telencephalic and brainstem afferents. Neuroscience 95:933–952

    PubMed  CAS  Google Scholar 

  • Sarter M, Bruno JP (2004) Developmental origins of the age-related decline in cortical cholinergic function and associated cognitive abilities. Neurobiol Aging 25:1127–1139

    PubMed  CAS  Google Scholar 

  • Schrijver NCA, Bahr NI, Weiss IC, Würbel H (2002) Dissociable effects of isolation rearing and environmental enrichment on exploration, spatial learning and HPA activity in adult rats. Pharmacol Biochem Behav 73:209–224

    PubMed  CAS  Google Scholar 

  • Segovia G, Mora F (2005) Effects of the metabotropic glutamate receptor agonist, ACPD, on the extracellular concentrations of GABA and acetylcholine in the prefrontal cortex of the rat during the normal process of aging. Brain Res Bull 65:11–16

    PubMed  CAS  Google Scholar 

  • Segovia G, Porras A, Del Arco A, Mora F (2001) Glutamatergic neurotransmission in aging: a critical perspective. Mech Ageing Dev 122:1–29

    PubMed  CAS  Google Scholar 

  • Segovia G, Yagüe AG, García-Verdugo JM, Mora F (2006) Environmental enrichment promotes neurogenesis and changes the extracellular concentrations of glutamate and GABA in the hippocampus of aged rats. Brain Res Bull 70:8–14

    PubMed  CAS  Google Scholar 

  • Segovia G, Del Arco A, De Blas M, Garrido P, Mora F (2008a) Effects of an enriched environment on the release of dopamine in the prefrontal cortex produced by stress and on working memory during aging in the awake rat. Behav Brain Res 187:304–311

    PubMed  CAS  Google Scholar 

  • Segovia G, Del Arco A, Garrido P, De Blas M, Mora F (2008b) Environmental enrichment reduces the response to stress of the cholinergic system in the prefrontal cortex during aging. Neurochem Int 52:1198–1203

    PubMed  CAS  Google Scholar 

  • Seif GI, Clements KM, Wainwright PE (2004) Effects of distraction and stress on delayed matching-to-place performance in aged rats. Physiol Behav 82:477–487

    PubMed  CAS  Google Scholar 

  • Stawski RS, Sliwinski MJ, Smyth JM (2006) Stress-related cognitive interference predicts cognitive function in old age. Psychol Aging 21:535–544

    PubMed  Google Scholar 

  • Stemmelin J, Lazarus C, Cassel S, Kelche C, Cassel J-C (2004) Immunohistochemical and neurochemical correlates of learning deficits in aged rats. Neuroscience 96:275–289

    Google Scholar 

  • Stevenson CW, Gratton A (2003) Basolateral amygdala modulation of the nucleus accumbens dopamine response to stress: role of the medial prefrontal cortex. Eur J Neurosci 17:1287–1295

    PubMed  CAS  Google Scholar 

  • Takahata R, Moghaddam B (1998) Glutamatergic regulation of basal and stimulus-activated dopamine release in the prefrontal cortex. J Neurochem 71:1443–1449

    Article  PubMed  CAS  Google Scholar 

  • Tanila H, Taira T, Piepponen TP, Honkanen A (1994) Effect of sex and age on brain monoamines and spatial learning in rats. Neurobiol Aging 15:733–741

    PubMed  CAS  Google Scholar 

  • Terry RD, Katzman R (2001) Life span and synapses: will there be a primary senile dementia? Neurobiol Aging 22:347–348

    PubMed  CAS  Google Scholar 

  • Thierry AM, Tassin JP, Blanc G, Glowinski J (1976) Selective activation of mesocortical DA system by stress. Nature 263:242–244

    PubMed  CAS  Google Scholar 

  • Tzschentke TM (2001) Pharmacology and behavioral pharmacology of the mesocortical dopamine system. Prog Neurobiol 63:241–320

    PubMed  CAS  Google Scholar 

  • van Gelder BM, Tijhuis MAR, Kalmijn S, Giampaoli S, Nissinen A, Kromhout D (2004) Physical activity in relation to cognitive decline in elderly men: the FINE study. Neurology 63:2316–2321

    PubMed  Google Scholar 

  • van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198

    PubMed  Google Scholar 

  • Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51:32–58

    PubMed  CAS  Google Scholar 

  • Wagner AK, Chen X, Kline AE, Li Y, Zafonte RD, Dixon CE (2005) Gender and environmental enrichment impact dopamine transporter expression after experimental traumatic brain injury. Exp Neurol 195:475–483

    PubMed  CAS  Google Scholar 

  • Wenk GL, Pierce DJ, Struble RG, Price DL, Corks LC (1989) Aged-related changes in the multiple neurotransmitter systems in the monkey brain. Neurobiol Aging 10:11–19

    PubMed  CAS  Google Scholar 

  • Williams GV, Castner SA (2006) Under the curve: critical issues for elucidating D1 receptor function in working memory. Neuroscience 139:263–276

    PubMed  CAS  Google Scholar 

  • Wilson RS, Mendes de Leon CF, Barnes LL, Schneider JA, Bienias JL, Evans DA, Bennett DA (2002) Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA 287:742–748

    PubMed  Google Scholar 

  • Wood DA, Buse JE, Wellman CL, Rebec GV (2005) Differential environmental exposure alters NMDA but not AMPA receptor subunit expression in nucleus accumbens core and shell. Brain Res 1042:176–183

    PubMed  CAS  Google Scholar 

  • Zaborszky L, Gaykema RP, Swanson DJ, Cullinan WE (1997) Cortical input to the basal forebrain. Neuroscience 79:1051–1078

    PubMed  CAS  Google Scholar 

  • Zhu J, Green T, Bardo MT, Dwoskin LP (2004) Environmental enrichment enhances sensitization to GBR 12935-induced activity and decreases dopamine transporter function in the medial prefrontal cortex. Behav Brain Res 148:107–117

    PubMed  CAS  Google Scholar 

  • Zhu J, Apparsundaram S, Bardo MT, Dwoskin LP (2005) Environmental enrichment decreases cell surface expression of the dopamine transporter in rat medial prefrontal cortex. J Neurochem 93:1434–1443

    PubMed  CAS  Google Scholar 

  • Zimmermann A, Stauffacher M, Langhans W, Wurbel H (2001) Enrichment-dependent differences in novelty exploration in rats can be explained by habituation. Behav Brain Res 121:11–20

    PubMed  CAS  Google Scholar 

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Acknowledgments

The studies reported in this article have been supported by the Spanish Ministry of Science and Technology DGICYT (SAF2000-0112, SAF2003-0448 and SAF2006-01554), the Comunidad Autónoma de Madrid (CAM 08.5/0020.1/03), and the University Complutense (PR45/05/14199/UCM). The authors thank the collaboration and technical assistance of Pedro Garrido, Marta de Blas, and Angela Amores.

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Correspondence to Gregorio Segovia.

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Dedicated to the special issue on Brain Plasticity, Prof. Fuxe.

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Segovia, G., Arco, A.d. & Mora, F. Environmental enrichment, prefrontal cortex, stress, and aging of the brain. J Neural Transm 116, 1007–1016 (2009). https://doi.org/10.1007/s00702-009-0214-0

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