Skip to main content
Log in

Depression-like behavior is dependent on age in male SAMP8 mice

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

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

    PubMed  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Blazer D (1989) Depression in the elderly. N Engl J Med 320:164–166

    Article  PubMed  CAS  Google Scholar 

  • Blier P, de Montigny C (1994) Current advances and trends in the treatment of depression. Trends Pharmacol Sci 15(7):220–226

    Article  PubMed  CAS  Google Scholar 

  • Bourin M, Baker GB (1996) The future of antidepressants. Biomed Pharmacother 50(1):7–12

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Kimpton J (2012) The brain derived neurotrophic factor and influences of stress in depression. Psychiatr Danub 24(Suppl 1):S169–S171

    PubMed  Google Scholar 

  • 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

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Lotrich F (2012) Inflammatory cytokines, growth factors, and depression. Curr Pharm Des 18(36):5920–5935

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto M (1997) Characteristics of age-related behavioral changes in senescence accelerated mouse SAM-P8 and SAM-P10. Exp Gerontol 32:139–148

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Murray CJ, Lopez AD (1997) Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet 349(9063):1436–1442

    Article  PubMed  CAS  Google Scholar 

  • Nutt DJ (2006) The role of dopamine and norepinephrine in depression and antidepressant treatment. J Clin Psychiatry 67(Suppl 6):3–8

    PubMed  CAS  Google Scholar 

  • O’Neil MF, Moore NA (2003) Animal models of depression: are there any? Hum Psychopharmacol Clin Exp 18:239–254

    Article  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Owens MJ, Nemeroff CB (1998) The serotonin transporter and depression. Depress Anxiety 8(Suppl 1):5–12

    Article  PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science 210(4465):88–90

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Polter AM, Li X (2011) Glycogen synthase kinase-3 is an intermediate modulator of serotonin neurotransmission. Front Mol Neurosci 4:31

    Article  PubMed  CAS  Google Scholar 

  • Porsolt RD (2000) Animal models of depression: utility for transgenic research. Rev Neurosci 11:53–58

    PubMed  CAS  Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Smith GW (1991) Recognition and treatment of depression in the elderly. J Clin Psychiatry 52:111–122

    Google Scholar 

  • Stockmeier CA (1997) Neurobiology of serotonin in depression and suicide. Ann N Y Acad Sci 836:220–232

    Article  PubMed  CAS  Google Scholar 

  • Takeda T (2009) Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice. Neurochem Res 34(4):639–659

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • 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

    CAS  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to E. Escubedo.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-013-9420-0

Keywords

Navigation