Abstract
Aging is associated with an increased risk of depression in humans. To elucidate the underlying mechanisms of depression and its dependence on aging, here we study signs of depression in male SAMP8 mice. For this purpose, we used the forced swimming test (FST). The total floating time in the FST was greater in SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not observed in 12-month-old mice, when both strains are considered elderly. Of the two strains, only the SAMP8 animals responded to imipramine treatment. We also applied the dexamethasone suppression test (DST) and studied changes in the dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in the cortex, and levels of TPH2. The DST showed a significant difference between SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8 mice presented depression-like behavior that is dependent on senescence process, because it differs from SAMR1, senescence resistant strain.
Similar content being viewed by others
References
Alvarez-López MJ, Castro-Freire M, Cosín-Tomás M, Sanchez-Roige S, Lalanza JF, Del Valle J, Párrizas M, Camins A, Pallás M, Escorihuela RM, Kaliman P (2013) Long-term exercise modulates hippocampal gene expression in senescent female mice. J Alzheimers Dis 33(4):1177–1190. doi:10.3233/JAD-121264
Arango V, Ernsberger P, Marzuk PM, Chen JS, Tierney H, Stanley M, Reis DJ, Mann JJ (1990) Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 47(11):1038–1047
Aznar S, Klein AB, Santini MA, Knudsen GM, Henn F, Gass P, Vollmayr B (2010) Aging and depression vulnerability interaction results in decreased serotonin innervation associated with reduced BDNF levels in hippocampus of rats bred for learned helplessness. Synapse 64(7):561–565
Blazer D (1989) Depression in the elderly. N Engl J Med 320:164–166
Blier P, de Montigny C (1994) Current advances and trends in the treatment of depression. Trends Pharmacol Sci 15(7):220–226
Bourin M, Baker GB (1996) The future of antidepressants. Biomed Pharmacother 50(1):7–12
Buddenberg TE, Komorowski M, Ruocco LA, Silva MA, Topic B (2009) Attenuating effects of testosterone on depressive-like behavior in the forced swim test in healthy male rats. Brain Res Bull 79:182–186
Butterfield DA, Poon HF (2005) The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer’s disease. Exp Gerontol 40(10):774–783
Canudas AM, Gutierrez-Cuesta J, Rodríguez MI, Acuña-Castroviejo D, Sureda FX, Camins A, Pallàs M (2005) Hyperphosphorylation of microtubule-associated protein tau in senescence-accelerated mouse (SAM). Mech Ageing Dev 126(12):1300–1304
Carrol BJ, Feiberg M, Greden JF, Tarika J, Albala AA, Haskett RF, James NM, Kronfol Z, Lohr N, Steine M, de Vigne JP, Young E (1981) A specific laboratory test for the diagnosis of melancholia: standardization, validation and clinical utility. Arch Gen Psychiatry 38:15–22
Casadesús G, Gutierrez-Cuesta J, Lee HG, Jiménez A, Tajes M, Ortuño-Sahagún D, Camins A, Smith MA, Pallàs M (2012) Neuronal cell cycle re-entry markers are altered in the senescence accelerated mouse P8 (SAMP8). J Alzheimers Dis 30(3):573–583
Chen WQ, Ma H, Bian JM, Zhang YZ, Li J (2012) Hyper-phosphorylation of GSK-3β: possible roles in chlorpyrifos-induced behavioral alterations in animal model of depression. Neurosci Lett 0304–3940(12):01178. doi:10.1016/j.neulet.2012.08.084
Chipana C, Camarasa J, Pubill D, Escubedo E (2006) Protection against MDMA-induced dopaminergic neurotoxicity in mice by methyllycaconitine: involvement of nicotinic receptors. Neuropharmacology 51(4):885–895
Duncan MJ, Crafton CJ, Wheeler DL (2000) Aging regulates 5-HT(1B) receptors and serotonin reuptake sites in the SCN. Brain Res 856(1–2):213–219
Flood JF, Farr SA, Uezu K, Morley JE (1998) Age-related changes in septal serotonergic, GABAergic and glutamatergic facilitation of retention in SAMP8 mice. Mech Ageing Dev 105(1–2):173–188
Gareri P, De Fazio P, De Sarro G (2002) Neuropharmacology of depression in aging and age-related diseases. Ageing Res Rev 1(1):113–134
Gourley SL, Taylor JR (2009) Recapitulation and reversal of a persistent depression-like syndrome in rodents. Curr Protoc Neurosci. Chapter 9: Unit 9.32
Groves JO (2007) Is it time to reassess the BDNF hypothesis of depression? Mol Psychiatry 12(12):1079–1088
Gutierrez-Cuesta J, Tajes M, Jimenez A, Coto-Montes A, Camins A, Pallàs M (2008) Evaluation of potential pro-survival pathways regulated by melatonin in a murine senescence model. J Pineal Res 45:497–505
Ida Y, Tanaka M, Tsuda A, Tsujimaru S, Nagasaki N (1985) Attenuating effect of diazepam on stress-induced increases in noradrenalin turnover in specific brain regions of rats: antagonism by Ro 15–1788. Life Sci 37:2491–2498
Iijima M, Ito A, Kurosu S, Chaki S (2010) Pharmacological characterization of repeated corticosterone injection-induced depression model in rats. Brain Res 1359:75–80
Karasawa N, Yamawaki Y, Nagatsu T, Kawase T, Nishiyama K, Watanabe K, Onozuka M, Nagatsu I (1999) Age-associated changes in the dopamine synthesis as determined by GTP cyclohydrolase I inhibitor in the brain of senescence-accelerated mouse-prone inbred strains (SAMP8). Neurosci Res 35(1):31–36
Kimpton J (2012) The brain derived neurotrophic factor and influences of stress in depression. Psychiatr Danub 24(Suppl 1):S169–S171
Kitamura Y, Zhao XH, Ohnuki T, Takei M, Nomura Y (1989) Ligand-binding characteristics of [3H]QNB, [3H]prazocin, [3H]rauwolsine, [3H]TCP and [3H]nitrendipine to cerebral cortical and hippocampal membranes of senescence-accelerated mouse. Neurosci Lett 196:334–338
Klein AB, Santini MA, Aznar S, Knudsen GM, Rios M (2010) Changes in 5-HT2A-mediated behavior and 5-HT2A- and 5-HT1A receptor binding and expression in conditional brain-derived neurotrophic factor knock-out mice. Neuroscience 169(3):1007–1016
Kumar R, Jorm AF, Parslow RA, Sachdev PS (2006) Depression in mild cognitive impairment in a community sample of individuals 60–64 years old. Int Psychogeriatr 18(3):471–480
Lotrich F (2012) Inflammatory cytokines, growth factors, and depression. Curr Pharm Des 18(36):5920–5935
Mann JJ, Stanley M, McBride PA, McEwen BS (1986) Increased serotonin 2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43(10):954–959
Miyamoto M (1997) Characteristics of age-related behavioral changes in senescence accelerated mouse SAM-P8 and SAM-P10. Exp Gerontol 32:139–148
Miyamoto M, Kiyota Y, Yamazaki N, Nagaoka A, Matsuo T, Nagawa Y, Takeda T (1986) Age-related changes in learning and memory in the senescence-accelerated mouse (SAM). Physiol Behav 38(3):399–406
Miyamoto M, Kiyota Y, Nishiyama M, Nagaoka A (1992) Senescence-accelerated mouse (SAM), age-related reduced anxiety-like behavior in the SAM-P/8 strain. Physiol Behav 51(5):979–985
Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet 349(9063):1436–1442
Nutt DJ (2006) The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 67(Suppl 6):3–8
O’Neil MF, Moore NA (2003) Animal models of depression: are there any? Hum Psychopharmacol Clin Exp 18:239–254
Okuma Y, Murayama T, Tha KK, Yamada C, Hosokawa M, Ishikawa A, Watanabe R, Maekawa M, Nomura Y (2000) Learning deficiency and alterations in acetylcholine receptors and protein kinase C in the brain of senescence-accelerated mouse (SAM)-P10. Mech Ageing Dev 114(3):191–199
Onodera T, Watanabe R, Tha KK, Hayashi Y, Murayama T, Okuma Y, Ono C, Oketani Y, Hosokawa M, Nomura Y (2000) Depressive behavior and alterations in receptors for dopamine and 5-hydroxytryptamine in the brain of the senescence-accelerated mouse (SAM)-P10. Jpn J Pharmacol 83:312–318
Owens MJ, Nemeroff CB (1998) The serotonin transporter and depression. Depress Anxiety 8(Suppl 1):5–12
Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D (2006) Depression and risk for Alzheimer disease, systematic review, meta-analysis, and meta regression analysis. Arch Gen Psychiatry 63:530–538
Peroutka SJ, Snyder SH (1980) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science 210(4465):88–90
Petursdottir AL, Farr SA, Morley JE, Banks WA, Skuladottir GW (2007) Lipid peroxidation in brain during aging in the senescence-accelerated mouse (SAM). Neurobiol Aging 28:1170–1178
Polter AM, Li X (2011) Glycogen synthase kinase-3 is an intermediate modulator of serotonin neurotransmission. Front Mol Neurosci 4:31
Porsolt RD (2000) Animal models of depression: utility for transgenic research. Rev Neurosci 11:53–58
Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732
Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47(4):379–391
Potter GG, Wagner HR, Burke JR, Plassman BL, Welsh-Bohmer KA, Steffens DC (2012) Neuropsychological predictors of dementia in late-life major depressive disorder. Am J Geriatr Psychiatry. doi:10.1097/JGP.0b013e318248764e
Shimada A, Ohta A, Akiguchi I, Takeda T (1992) Inbred SAM-P/10 as a mouse model of spontaneous, inherited brain atrophy. J Neuropathol Exp Neurol 51:440–450
Shimada A, Ohta A, Akiguchi I, Takeda T (1993) Age-related deterioration in conditional avoidance task in the SAM-P/10 mouse, an animal model of spontaneous brain atrophy. Brain Res 608:266–272
Smith GW (1991) Recognition and treatment of depression in the elderly. J Clin Psychiatry 52:111–122
Stockmeier CA (1997) Neurobiology of serotonin in depression and suicide. Ann N Y Acad Sci 836:220–232
Takeda T (2009) Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice. Neurochem Res 34(4):639–659
Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T, Tomita Y, Yasuhira K, Hamamoto H, Shimizu K, Ishii M, Yamamuro T (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17(2):183–194
Takeda T, Hosokawa M, Higuchi K (1991) Senescence-accelerated mouse (SAM): a novel murine model of accelerated senescence. J Am Geriatr Soc 39(9):911–919
Waider J, Araragi N, Gutknecht L, Lesch KP (2011) Tryptophan hydroxylase-2 (TPH2) in disorders of cognitive control and emotion regulation: a perspective. Psychoneuroendocrinology 36:393–405
Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN (1990) 5HT2 receptor changes in major depression. Biol Psychiatry 27(5):489–496
Zhao XH, Nomura Y (1990) Age-related changes in uptake and release on L-[3H]noradrenaline in brain slices of senescence accelerated mouse. Int J Dev 8(3):267–272
Acknowledgments
We thank the Language Advisory Service of the University of Barcelona for revising the manuscript. This study was supported by Grants SAF2010-15948, SAF2011-2363 and SAF2012-39852 from the “Ministerio de Educación y Ciencia”; Plan Nacional sobre Drogas (2010/005); 2009/SGR977 and 2009/SGR00893 from the “Generalitat de Catalunya” and 610RT0405 from the Programa Iberoamericano de Ciencia y Tecnologia para el Desarrollo (CYTED).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pérez-Cáceres, D., Ciudad-Roberts, A., Rodrigo, M.T. et al. Depression-like behavior is dependent on age in male SAMP8 mice. Biogerontology 14, 165–176 (2013). https://doi.org/10.1007/s10522-013-9420-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-013-9420-0