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Nine-month-long Social Isolation Changes the Levels of Monoamines in the Brain Structures of Rats: A Comparative Study of Neurochemistry and Behavior

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Abstract

Social isolation (SI) is chronic psycho-emotional stress for humans and other socially living species. There are few comparative studies that have measured monoamine levels in brain structures in male and female rats subjected to SI. Existing data is highly controversial. In our recent study, we investigated behavioral effects of SI prolonged up to 9 months on a rather large sample of 69 male and female Wistar rats. In the present study, we measured the levels of monoamines—norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), and DA and 5-HT metabolites—in the brain structures of 40 rats from the same sample. The single-housed rats of both sexes showed hyperactivity and reduced reactivity to novelty in the Open Field test, and impaired passive avoidance learning. Regardless of their sex, by the time of sacrifice, the single-housed rats weighed less and had lower pain sensitivity and decreased anxiety compared with group-housed animals. SI decreased NE levels in the hippocampus and increased them in the striatum. SI induced functional activation of the DA-ergic system in the frontal cortex and hypothalamus, with increased DA and 3-methoxytyramine levels. SI-related changes were found in the 5-HT-ergic system: 5-HT levels increased in the frontal cortex and striatum, while 5-hydroxyindoleacetic acid only increased in the frontal cortex. We believe that SI prolonged for multiple months could be a valuable model for comparative analysis of the behavioral alterations and the underlying molecular processes in dynamics of adaptation to chronic psychosocial stress in male and female rats in relation to age-dependent changes.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Chen P, Hong W (2018) Neural circuit mechanisms of social behavior. Neuron 98(1):16–30. https://doi.org/10.1016/j.neuron.2018.02.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mumtaz F, Khan MI, Zubair M, Dehpour AR (2018) Neurobiology and consequences of social isolation stress in animal model — a comprehensive review. Biomed Pharmacother 105:1205–1222. https://doi.org/10.1016/j.biopha.2018.05.086

    Article  CAS  PubMed  Google Scholar 

  3. Schweinfurth MK (2020) The social life of Norway rats (Rattus norvegicus). Elife 9:e54020. https://doi.org/10.7554/eLife.54020

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fone KCF, Porkess MV (2008) Behavioural and neurochemical effects of post-weaning social isolation in rodents - relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev 32(6):1087–1102. https://doi.org/10.1016/j.neubiorev.2008.03.003

    Article  CAS  PubMed  Google Scholar 

  5. Walker DM, Cunningham AM, Gregory JK, Nestler EJ (2019) Long-term behavioral effects of post-weaning social isolation in males and females. Front Behav Neurosci 13:66. https://doi.org/10.3389/fnbeh.2019.00066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Arzate-Mejía RG, Lottenbach Z, Schindler V, Jawaid A, Mansuy IM (2020) Long-term impact of social isolation and molecular underpinnings. Front Genet 22(11):589621. https://doi.org/10.3389/fgene.2020.589621

    Article  CAS  Google Scholar 

  7. Krupina NA, Khlebnikova NN, Orlova IN (2015) Early social isolation increases aggression and impairs a short-term habituation in acoustic startle reflex in rats Patol Fiziol Eksp Ter 59(4):4–12 (In Russian). PMID: 27116871

    CAS  PubMed  Google Scholar 

  8. Khlebnikova NN, Medvedeva YS, Krupina NA (2018) Early social isolation causing emotional motivational alterations in rats, is accompanied by a deficit of short-term habituation, but does not affect spatial memory. Zh Vyssh Nervn Deyat 68:646–662 (In Russian). https://doi.org/10.1134/S0044467718050052

    Article  Google Scholar 

  9. Grigoryan GA, Pavlova IV, Zaichenko MI (2022) Effects of social isolation on the development of anxiety and depression-like behavior in model experiments in animals. Neurosci Behav Physiol 52(5):722–738. https://doi.org/10.1007/s11055-022-01297-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Shirenova SD, Khlebnikova NN, Krupina NA (2023) Changes in sociability and preference for social novelty in female rats in prolonged social isolation. Neurosci Behav Physiol 1(23): Article 14 (In Press)

  11. Begni V, Sanson A, Pfeiffer N et al (2020) Social isolation in rats: Effects on animal welfare and molecular markers for neuroplasticity. PLoS ONE 15(10):e0240439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hall FS (1998) Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences. Crit Rev Neurobiol 12(1–2):129–162. https://doi.org/10.1615/critrevneurobiol.v12.i1-2.50

    Article  CAS  PubMed  Google Scholar 

  13. Liu N, Wang Y, An AY, Banker Ch, Qian Y-H, O’Donnell JM (2020) Single housing-induced effects on cognitive impairment and depression-like behavior in male and female mice involve neuroplasticity-related signaling. Eur J Neurosci 52(1):2694–2704. https://doi.org/10.1111/ejn.14565

    Article  PubMed  Google Scholar 

  14. Lukkes JL, Watt MJ, Lowry CA, Forster GL (2009) Consequences of post-weaning social isolation on anxiety behavior and related neural circuits in rodents. Front Behav Neurosci 3:18. https://doi.org/10.3389/neuro.08.018.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rivera-Irizarry JK, Skelly MJ, Pleil KE (2020) Social isolation stress in adolescence, but not adulthood, produces hypersocial behavior in adult male and female c57bl/6j mice. Front Behav Neurosci 14:129. https://doi.org/10.3389/fnbeh.2020.00129

    Article  PubMed  PubMed Central  Google Scholar 

  16. Einon DF, Morgan MJ (1977) A critical period for social isolation in the rat. Devl Psychobiol 10(2):123–132. https://doi.org/10.1002/dev.420100205

    Article  CAS  Google Scholar 

  17. Whitaker LR, Degoulet M, Morikawa H (2013) Social deprivation enhances VTA synaptic plasticity and drug-induced contextual learning. Neuron 77(2):335–345. https://doi.org/10.1016/j.neuron.2012.11.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Noisin EL, Thomas WE (1988) Ontogeny of dopaminergic function in the rat midbrain tegmentum, corpus striatum and frontal cortex. Dev Brain Res 41(1–2):241–252. https://doi.org/10.1016/0165-3806(88)90186-1

    Article  CAS  Google Scholar 

  19. Suri D, Teixeira CM, Cagliostro MK, Mahadevia D, Ansorge MS (2015) Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology 40(1):88–112. https://doi.org/10.1038/npp.2014.231

    Article  PubMed  Google Scholar 

  20. Hamon M, Blier P (2013) Monoamine neurocircuitry in depression and strategies for new treatments. Prog NeuroPsychopharmacol Bioll Psychiatry 45:54–63. https://doi.org/10.1016/j.pnpbp.2013.04.009

    Article  CAS  Google Scholar 

  21. Hu H (2016) Reward and aversion. Annu Rev Neurosci 39(1):297–324. https://doi.org/10.1146/annurev-neuro-070815-014106

    Article  CAS  PubMed  Google Scholar 

  22. Miura H, Qiao H, Ohta T (2002) Influence of aging and social isolation on changes in brain monoamine turnover and biosynthesis of rats elicited by novelty stress. Synapse 46(2):116–124. https://doi.org/10.1002/syn.10133

    Article  CAS  PubMed  Google Scholar 

  23. Brenes JC, Fornaguera J (2009) The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum. Behav Brain Res 198(1):199–205. https://doi.org/10.1016/j.bbr.2008.10.036

    Article  CAS  PubMed  Google Scholar 

  24. Trabace L, Zotti M, Colaianna M, Morgese MG, Schiavone S, Tucci P, Harvey BH, Wegener G, Cuomo V (2012) Neurochemical differences in two rat strains exposed to social isolation rearing. Acta Neuropsychiatr 24(5):286–295. https://doi.org/10.1111/j.1601-5215.2011.00627.x

    Article  PubMed  Google Scholar 

  25. Bickerdike MJ, Wright IK, Marsden CA (1993) Social isolation attenuates rat forebrain 5-HT release induced by KCI stimulation and exposure to a novel environment. Behav Pharmacol 4(3):231–236. https://doi.org/10.1097/00008877-199306000-00005

    Article  CAS  PubMed  Google Scholar 

  26. Weinstock M, Speiser Z, Ashkenazi R (1978) Changes in brain catecholamine turnover and receptor sensitivity induced by social deprivation in rats. Psychopharmacology 56(2):205–209. https://doi.org/10.1007/BF00431851

    Article  CAS  PubMed  Google Scholar 

  27. Howes SR, Dalley JW, Morrison CH, Robbins TW, Everitt BJ (2000) Leftward shift in the acquisition of cocaine self-administration in isolation-reared rats: relationship to extracellular levels of dopamine, serotonin and glutamate in the nucleus accumbens and amygdala-striatal FOS expression. Psychopharmacology 151(1):55–63. https://doi.org/10.1007/s002130000451

    Article  CAS  PubMed  Google Scholar 

  28. Mncube K, Möller M, Harvey BH (2021) Post-weaning social isolated flinders sensitive line rats display bio-behavioural manifestations resistant to fluoxetine: a model of treatment-resistant depression. Front Psychiatry 12:688150. https://doi.org/10.3389/fpsyt.2021.688150

    Article  PubMed  PubMed Central  Google Scholar 

  29. Holson RR, Ali SF, Scallet AC (1988) The effect of isolation rearing and stress on monoamines in forebrain nigrostriatal, mesolimbic, and mesocortical dopamine systems. Ann N Y Acad Sci 537:512–514. https://doi.org/10.1111/j.1749-6632.1988.tb42143.x

    Article  Google Scholar 

  30. Heidbreder CA, Weiss IC, Domeney AM, Pryce C, Homberg J, Hedou G, Feldon J, Moran MC, Nelson P (2000) Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome. Neuroscience 100:749–768. https://doi.org/10.1016/s0306-4522(00)00336-5

    Article  CAS  PubMed  Google Scholar 

  31. Jones GH, Hernandez TD, Kendall DA, Marsden CA, Robbins TW (1992) Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry. Pharmacol Biochem Behav 43(1):17–35. https://doi.org/10.1016/0091-3057(92)90635-s

    Article  CAS  PubMed  Google Scholar 

  32. Ko C-Y, Liu Y-P (2016) Disruptions of sensorimotor gating, cytokines, glycemia, monoamines, and genes in both sexes of rats reared in social isolation can be ameliorated by oral chronic quetiapine administration. Brain Behav Immun 51:119–130. https://doi.org/10.1016/j.bbi.2015.08.003

    Article  CAS  PubMed  Google Scholar 

  33. Powell SB, Geyer MA, Preece MA, Pitcher LK, Reynolds GP, Swerdlow NR (2003) Dopamine depletion of the nucleus accumbens reverses isolation-induced deficits in prepulse inhibition in rats. Neuroscience 119:233–240. https://doi.org/10.1016/s0306-4522(03)00122-2

    Article  CAS  PubMed  Google Scholar 

  34. Thoa NB, Tizabi Y, Jacobowitz DM (1977) The effect of isolation on catecholamine concentration and turnover in discrete areas of the rat brain. Brain Res 131(2):259–269. https://doi.org/10.1016/0006-8993(77)90519-4

    Article  CAS  PubMed  Google Scholar 

  35. Jaffe EH, De Frias V, Ibarra C (1993) Changes in basal and stimulated release of endogenous serotonin from different nuclei of rats subjected to two models of depression. Neurosci Lett 162(1–2):157–160. https://doi.org/10.1016/0304-3940(93)90584-8

    Article  CAS  PubMed  Google Scholar 

  36. Karkhanis AN, Locke JL, McCoo BA, Weiner JL, Jones SR (2014) Social isolation rearing increases nucleus accumbens dopamine and norepinephrine responses to acute ethanol in adulthood. Alcohol Clin Exp Res 38:2770–2779. https://doi.org/10.1111/acer.12555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Karkhanis AN, Alexander NJ, McCool BA, Weiner JL, Jones SR (2015) Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala. Synapse 69(8):385–395. https://doi.org/10.1002/syn.21826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Brenes JC, Fornaguera J (2009) The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum. Behav Brain Res 198(1):199–205. https://doi.org/10.1016/j.bbr.2008.10.036

    Article  CAS  PubMed  Google Scholar 

  39. Brenes JC, Fornaguera J, Sequeira-Cordero A (2020) Environmental enrichment and physical exercise attenuate the depressive-like effects induced by social isolation stress in rats. Front Pharmacol 11:804. https://doi.org/10.3389/fphar.2020.00804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Miura H, Qiao H, Ohta T (2002) Influence of aging and social isolation on changes in brain monoamine turnover and biosynthesis of rats elicited by novelty stress. Synapse 46(2):116–124. https://doi.org/10.1002/syn.10133

    Article  CAS  PubMed  Google Scholar 

  41. Gambardella P, Greco AM, Sticchi R, Bellotti R, Di Renzo G (1994) Individual housing modulates daily rhythms of hypothalamic catecholaminergic system and circulating hormones in adult male rats. Chronobiol Int 11(4):213–221. https://doi.org/10.3109/07420529409067790

    Article  CAS  PubMed  Google Scholar 

  42. Krupina NA, Khlebnikova NN, Narkevich VB, Naplekova PL, Kudrin VS (2020) The levels of monoamines and their metabolites in the brain structures of rats subjected to two- and three-month-long social isolation. Bull Exp Biol Med 168(5):605–609. https://doi.org/10.1007/s10517-020-04761-5

    Article  CAS  PubMed  Google Scholar 

  43. Krupina NA, Shirenova SD, Khlebnikova NN (2020) Prolonged social isolation, started early in life, impairs cognitive abilities in rats depending on sex. Brain Sci 10(11):799. https://doi.org/10.3390/brainsci10110799

    Article  PubMed  PubMed Central  Google Scholar 

  44. Patel D, Kas MJ, Chattarji S, Buwalda B (2019) Rodent models of social stress and neuronal plasticity: relevance to depressive-like disorders. Behav Brain Res 369:111900. https://doi.org/10.1016/j.bbr.2019.111900

    Article  PubMed  Google Scholar 

  45. Shipp S (2016) The functional logic of corticostriatal connections. Brain Struct Funct 222:1–38. https://doi.org/10.1007/s00429-016-1250-9

    Article  Google Scholar 

  46. Knight P, Chellian R, Wilson R, Behnood-Rod A, Panunzio S, Bruijnzeel AW (2021) Sex differences in the elevated plus-maze test and large open field test in adult Wistar rats. Pharmacol Biochem Behav 204:173168. https://doi.org/10.1016/j.pbb.2021.173168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hall FS, Humby T, Wilkinson L, Robbins T (1997) The Effects of isolation-rearing of rats on behavioural responses to food and environmental novelty. Physiol Behav 62:281–290. https://doi.org/10.1016/s0031-9384(97)00115-7

    Article  CAS  PubMed  Google Scholar 

  48. Hall FS, Huang S, Fong GW, Pert A, Linnoila M (1998) Effects of isolation-rearing on locomotion, anxiety and responses to ethanol in Fawn Hooded and Wistar rats. Psychopharmacology 139:203–209. https://doi.org/10.1007/s002130050705

    Article  CAS  PubMed  Google Scholar 

  49. Rodina VI, Krupina NA, Kryzhanovskii GN, Oknina NB (1992) A new method of evaluating anxiety states and phobias in rats. Bull Exp Biol Med 114:916–920. https://doi.org/10.1007/BF00790041

    Article  Google Scholar 

  50. Paxinos G, Watson Ch (2007) The rat brain in Stereotaxis coordinates. Sixth edition. Academic Press is an imprint of Elsevier. UK, The Niderlands, USA, p 446

    Google Scholar 

  51. Chiu K, Lau WM, Lau HT, So KF, Chang RCC (2007) Micro-dissection of rat brain for RNA or protein extraction from specific brain region. JoVE 7. http://www.jove.com/index/Details.stp?ID=269https://doi.org/10.3791/269

  52. Shirenova SD, Krupina NA, Khlebnikova NN (2019) Dynamics of pain sensitivity in male and female rats under prolonged social isolation. Russian J Pain 17(4):27–34 (In Russian). https://doi.org/10.25731/RASP.2019.04.38

    Article  Google Scholar 

  53. Cruz FC, Duarte JO, Leгo RM, Hummel LF, Planeta CS, Crestani CC (2016) Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation eduring adolescence. Dev Neurobiol 76(1):34–46. https://doi.org/10.1002/dneu.22297

    Article  CAS  PubMed  Google Scholar 

  54. Dulabi AN, Shakerin Z, Mehranfard N, Ghasemi M (2020) Vitamin C protects against chronic social isolation stress-induced weight gain and depressive-like behavior in adult male rats. Endocr Regul 54(4):266–274. https://doi.org/10.2478/enr-2020-0030

    Article  PubMed  Google Scholar 

  55. Maslova LN, Bulygina VV, Amstislavskaia TG (2009) Social isolation and social instability in adolescence in rats: Immediate and long-term physiological and behavioral effects. Zh Vyssh Nervn Deyat 59(5):598–609 (In Russian) PMID: 19947536

    CAS  Google Scholar 

  56. Sánchez MM, Aguado F, Sanchez-Toscano F, Saphier D (1998) Neuroendocrine and immunocytochemical demonstrations of decreased hypothalamo-pituitary-adrenal axis responsiveness to restraint stress after long-term social isolation. Endocrinology 139(2):579–587. https://doi.org/10.1210/endo.139.2.5720

    Article  PubMed  Google Scholar 

  57. Serra M, Marongiu F, Laconi E (2021) Long-term moderate caloric restriction and social isolation synergize to induce anorexia-like behavior in rats. Nutrition 86:111177. https://doi.org/10.1016/j.nut.2021.111177

    Article  PubMed  Google Scholar 

  58. Vrankova S, Galandakova Z, Benko J, Cebova M, Riecansky I, Pechanova O (2021) Duration of social isolation affects production of nitric oxide in the rat brain. Int J Mol Sci 22:10340. https://doi.org/10.3390/ijms221910340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Brenes Sáenz JC, Villagra OR, Fornaguera Trías J (2006) Factor analysis of forced swimming test, sucrose preference test and open field test on enriched, social and isolated reared rats. Behav Brain Res 169(1):57–65. https://doi.org/10.1016/j.bbr.2005.12.001

    Article  PubMed  Google Scholar 

  60. Slattery DA, Cryan JF (2012) Using the rat forced swim test to assess antidepressant-like activity in rodents. Nat Protoc 7:1009–1014. https://doi.org/10.1038/nprot.2012.044

    Article  CAS  PubMed  Google Scholar 

  61. Cryan JF, Markou A, Lucki I (2002) Assessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 23(5):238–245. https://doi.org/10.1016/s0165-6147(02)02017-5

    Article  CAS  PubMed  Google Scholar 

  62. West AP (1990) Neurobehavioral studies of forced swimming: the role of learning and memory in the forced swim test. Prog NeuroPsychopharmacol Biol Psychiatry 14(6):863–877. https://doi.org/10.1016/0278-5846(90)90073-p

    Article  CAS  PubMed  Google Scholar 

  63. Molendijk ML, de Kloet ER (2019) Coping with the forced swim stressor: current state-of-the-art. Behav Brain Res 364:1–10. https://doi.org/10.1016/j.bbr.2019.02.005

    Article  PubMed  Google Scholar 

  64. Trujillo V, Valentim-Lima E, Mencalha R, Carbalan QSR, Dos-Santos RC, Felintro V, Girardi СEN, Rorato R, Lustrino D, Reis LC, Mecawi AS (2020) Neonatal serotonin depletion induces hyperactivity and anxiolytic-like sex-dependent effects in adult rats. Mol Neurobiol 58(3):1036–1051. https://doi.org/10.1007/s12035-020-02181-0

    Article  CAS  PubMed  Google Scholar 

  65. Overstreet DH, Pucilowski O, Rezvani AH, Janowsky DS (1995) Administration of antidepressants, diazepam and psychomotor stimulants further confirms the utility of flinders sensitive line rats as an animal model of depression. Psychopharmacology 121:27–37. https://doi.org/10.1007/BF02245589

    Article  CAS  PubMed  Google Scholar 

  66. Bratch A, Kann S, Cain JA, Wu J-E, Rivera-Reyes N, Dalecki S, Arman D, Dunn A, Cooper Sh, Corbin HE, Doyle AR, Pizzo MJ, Smith AE, Crystal JD (2016) Working memory systems in the rat. Curr Biol 26(3):351–355. https://doi.org/10.1016/j.cub.2015.11.068

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Garzón J, Fuentes J, Del Rio J (1979) Antidepressants selectively antagonize the hyperactivity induced in rats by long-term isolation. Eur J Pharmacol 59(3–4):293–296. https://doi.org/10.1016/0014-2999(79)90293-0

    Article  PubMed  Google Scholar 

  68. Burke NN, Hayes E, Calpin P, Kerr DM, Moriarty O, Finn DP, Roche M (2010) Enhanced nociceptive responding in two rat models of depression is associated with alterations in monoamine levels in discrete brain regions. Neuroscience 171(4):1300–1313. https://doi.org/10.1016/j.neuroscience.2010.10.030

    Article  CAS  PubMed  Google Scholar 

  69. Amit Z, Galina ZH (1988) Stress Induced Analgesia plays an adaptive role in the organization of behavioral responding. Brain Res Bull 21(6):955–958. https://doi.org/10.1016/0361-9230(88)90033-0

    Article  CAS  PubMed  Google Scholar 

  70. Bagheri F, Goudarzi I, Lashkarbolouki T, Elahdadi Salmani M, Goudarzi A, Morley-Fletcher S (2022) The combined effects of perinatal ethanol and early-life stress on cognition and risk-taking behavior through oxidative stress in rats. Neurotox Res 40(4):925–940. https://doi.org/10.1007/s12640-022-00506-6

    Article  CAS  PubMed  Google Scholar 

  71. Lopez de Ceballos M, Guisado E, Sanchez-Blazqueq P, Garzon J, Del Rio J (1983) Long-term social isolation in the rat induces opposite changes in binding to α1- and α2-adrenoceptors in the brain and vas deferens. Neurosci Lett 39(2):217–222. https://doi.org/10.1016/0304-3940(83)90080-0

    Article  CAS  PubMed  Google Scholar 

  72. Fulford AJ, Marsden CA (1997) Effect of isolation-rearing on noradrenaline release in rat hypothalamus and hippocampus in vitro. Brain Res 748(1–2):93–99. https://doi.org/10.1016/s0006-8993(96)01279-6

    Article  CAS  PubMed  Google Scholar 

  73. Worbe Y, Baup N, Grabli D, Chaigneau M, Mounayar S, McCairn K, Féger J, Tremblay L (2009) Behavioral and movement disorders induced by local inhibitory dysfunction in primate striatum. Cereb Cortex 19(8):1844–1856. https://doi.org/10.1093/cercor/bhn214

    Article  PubMed  Google Scholar 

  74. Mei X, Wang L, Yang B, Li X (2021) Sex differences in noradrenergic modulation of attention and impulsivity in rats psychopharmacology. (Berl) 238(8):2167–2177. https://doi.org/10.1007/s00213-021-05841-8

    Article  CAS  Google Scholar 

  75. Krebs RM, Park HRP, Bombeke K, Boehler CN (2018) Modulation of locus coeruleus activity by novel oddball stimuli. Brain Imaging Behav 12(2):577–584. https://doi.org/10.1007/s11682-017-9700-4

    Article  PubMed  Google Scholar 

  76. Atmore KH, Stein DJ, Harvey BH, Russell VA, Howells FM (2020) Differential effects of social isolation rearing on glutamate- and GABA-stimulated noradrenaline release in the rat prefrontal cortex and hippocampus. Eur Neuropsychopharmacol 36:111–120. https://doi.org/10.1016/j.euroneuro.2020.05.007

    Article  CAS  PubMed  Google Scholar 

  77. Ramos BP, Arnsten AFT (2007) Adrenergic pharmacology and cognition: focus on the prefrontal cortex. Pharmacol Ther 113(3):523–536. https://doi.org/10.1016/j.pharmthera.2006.11

    Article  CAS  PubMed  Google Scholar 

  78. Dalley JW, Theobald DE, Pereira EA, Li PM, Robbins TW (2002) Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity. Psychopharmacology 164(3):329–340. https://doi.org/10.1007/s00213-002-1215-y

    Article  CAS  PubMed  Google Scholar 

  79. Cools R, Froböse M, Aarts E, Hofmans L (2019) Dopamine and the motivation of cognitive control. Handb Clin Nurol 163:123–143. https://doi.org/10.1016/b978-0-12-804281-6.00007-0

    Article  Google Scholar 

  80. Fitzgerald ML, Mackie K, Pickel VM (2013) The impact of adolescent social isolation on dopamine D2 and cannabinoid CB1 receptors in the adult rat prefrontal cortex. Neuroscience 235:40–50. https://doi.org/10.1016/j.neuroscience.2013.0

    Article  CAS  PubMed  Google Scholar 

  81. Nakazato T, Akiyama A (2002) Behavioral activity and stereotypy in rats induced by L-DOPA metabolites: a possible role in the adverse effects of chronic L-DOPA treatment of Parkinson’s disease. Brain Res 930(1–2):134–142. https://doi.org/10.1016/s0006-8993(02)02238-2

    Article  CAS  PubMed  Google Scholar 

  82. Sotnikova TD, Beaulieu J-M, Espinoza S, Masri B, Zhang X, Salahpour A, Barak LS, Caron MG, Gainetdinov RR (2010) The dopamine metabolite 3-methoxytyramine is a neuromodulator. PLoS ONE 5(10):e13452. https://doi.org/10.1371/journal.pone.0013452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Heck AL, Handa RJ (2019) Sex differences in the hypothalamic–pituitary–adrenal axis’ response to stress: an important role for gonadal hormones. Neuropsychopharmacology 44(1):45–58. https://doi.org/10.1038/s41386-018-0167-9

    Article  CAS  PubMed  Google Scholar 

  84. Muramatsu T, Inoue K, Iwasaki S, Yamauchi T, Hayashi T, Kiriike N (2006) Corticotropin-releasing factor receptor type 1, but not type 2, in the ventromedial hypothalamus modulates dopamine release in female rats. Pharmacol Biochem Behav 85(2):435–440. https://doi.org/10.1016/j.pbb.2006.09.013

    Article  CAS  PubMed  Google Scholar 

  85. Antkiewicz-Michaluk L, Ossowska K, Romańska I, Michaluk J, Vetulani J (2008) 3-Methoxytyramine, an extraneuronal dopamine metabolite plays a physiological role in the brain as an inhibitory regulator of catecholaminergic activity. Eur J Pharmacol 599(1–3):32–35. https://doi.org/10.1016/j.ejphar.2008.09.03

    Article  CAS  PubMed  Google Scholar 

  86. Del Arco A, Zhu S, Terasmaa A, Mohammed AH, Fuxe K (2003) Hyperactivity to novelty induced by social isolation is not correlated with changes in D2 receptor function and binding in striatum. Psychopharmacology 171(2):148–155. https://doi.org/10.1007/s00213-003-1578-8

    Article  CAS  PubMed  Google Scholar 

  87. Veenema AH (2009) Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models? Front Neuroendocrinol 30(4):497–518. https://doi.org/10.1016/j.yfrne.2009.03.003

    Article  CAS  PubMed  Google Scholar 

  88. Mahar I, Bambico FR, Mechawar N, Nobrega JN (2014) Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci Biobehav Rev 38:173–192. https://doi.org/10.1016/j.neubiorev.2013.11.0

    Article  CAS  PubMed  Google Scholar 

  89. Bacqué-Cazenave J, Bharatiya R, Barrière G, Delbecque J-P, Bouguiyoud N, Di Giovanni GD, Cattaert D, De Deurwaerdère PD (2020) Serotonin in animal cognition and behavior. Int J Mol Sci 21(5):1649. https://doi.org/10.3390/ijms21051649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Perez-Garcia G, Meneses A (2008) Memory formation, amnesia, improved memory and reversed amnesia: 5-HT role. Behav Brain Res 195(1):17–29. https://doi.org/10.1016/j.bbr.2007.11.027

    Article  CAS  PubMed  Google Scholar 

  91. Fillingim RB, Edwards RR (2005) Is self-reported childhood abuse history associated with pain perception among healthy young women and men? Clin J Pain 21(5):387–397. https://doi.org/10.1097/01.ajp.0000149801.46

    Article  PubMed  Google Scholar 

  92. Santarelli S, Zimmermann C, Kalideris G, Lesuis SL, Arloth J, Uribe A, Dournesa C, Balsevicha G, Hartmanna J, Masanaa M, Binderb EB, Spengle D, Schmidt MV (2017) An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology 78:213–221. https://doi.org/10.1016/j.psyneuen.2017.01.021

    Article  PubMed  Google Scholar 

  93. Zubkov EA, Zorkina YA, Orshanskaya EV, Khlebnikova NN, Krupina NA, Chekhonin VP (2019) Post-weaning social isolation disturbs gene expression in rat brain structures. Bull Exp Biol Med 166(3):364–368. https://doi.org/10.1007/s10517-019-04351-0

    Article  CAS  PubMed  Google Scholar 

  94. Bombardi C, Grandis A, Pivac N, Sagud M, Lucas G, Chagraoui A, Lemaire-Mayog V, De Deurwaerde` Ph G (2021) Serotonin modulation of hippocampal functions: From anatomy to neurotherapeutics. In: Giovanni G, De Deurwaerdere Ph (Eds) 5-HT interaction with other neurotransmitters: Experimental evidence and therapeutic relevance, 1st edn. © Elsevier 2021, Part B Ch 3, pp 83–158. https://doi.org/10.1016/bs.pbr.2021.01.031

  95. Lindenfors P, Gittleman JL, Jones KE (2007) Sexual size dimorphism in mammals. In: Fairbairn DJ, Blanckenhorn WU, Székely T (eds) Sex, size, and gender roles: evolutionary studies of sexual size dimorphism. Oxford University Press: Oxford, UK, pp 16–26. Ch. 2

  96. Sample CH, Davidson TL (2018) Considering sex differences in the cognitive controls of feeding. Physiol Behav 187:97–107. https://doi.org/10.1016/j.physbeh.2017.11.023

    Article  CAS  PubMed  Google Scholar 

  97. Hyde JF, Jerussi TP (1983) Sexual dimorphism in rats with respect to locomotor activity and circling behavior. Pharmacol Biochem Behav 18(5):725–729. https://doi.org/10.1016/0091-3057(83)90014-x

    Article  CAS  PubMed  Google Scholar 

  98. Fernandes C, González MI, Wilson CA, File SE (1999) Factor analysis shows that female rat behaviour is characterized primarily by activity, male rats are driven by sex and anxiety. Pharmacol Biochem Behav 64(4):731–738. https://doi.org/10.1016/s0091-3057(99)00139-2

    Article  CAS  PubMed  Google Scholar 

  99. Scholl JL, Afzal A, Fox LC, Watt MJ, Forster GL (2019) Sex differences in anxiety-like behaviors in rats. Physiol Behav 211:112670. https://doi.org/10.1016/j.physbeh.2019.11267

    Article  CAS  PubMed  Google Scholar 

  100. Kokras N, Pastromas N, Papasava D, de Bournonville C, Cornil CA, Dalla C (2018) Sex differences in behavioral and neurochemical effects of gonadectomy and aromatase inhibition in rats. Psychoneuroendocrinology 87:93–107. https://doi.org/10.1016/j.psyneuen.2017.10.007

    Article  CAS  PubMed  Google Scholar 

  101. Dearing C, Morano R, Ptaskiewicz E, Mahbod P, Scheimann JR, Franco-Villanueva A, Wulsin L, Myers B (2021) Glucoregulation and coping behavior after chronic stress in rats: sex differences across the lifespan. Horm Behav 136:105060. https://doi.org/10.1016/j.yhbeh.2021.105060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Albonetti ME, Farabollini F (1995) Effects of single restraint on the defensive behaviour of male and female rats. Physiol Behav 57:431–437. https://doi.org/10.1016/0031-9384(94)00272-7

    Article  CAS  PubMed  Google Scholar 

  103. Yezierski, RP (2012). The effects of age on pain sensitivity: pre-clinical studies. Pain Med 13(Suppl 2): S27–S36. https://doi.org/10.1111/j.1526-4637.2011.01311.x

  104. Gagliese L, Melzack R (2000) Age differences in nociception and pain behaviours in the rat. Neurosci Biobehav Rev 24:843–854. https://doi.org/10.1016/s0149-7634(00)00041-5

    Article  CAS  PubMed  Google Scholar 

  105. Boullon L, Finn DP, Llorente-Berzal Á (2021) Sex differences in a rat model of peripheral neuropathic pain and associated levels of endogenous cannabinoid ligands. Front Pain Res (Lausanne) 2:673638. https://doi.org/10.3389/fpain.2021.673638

    Article  PubMed  Google Scholar 

  106. Vierck ChJ, Acosta-Rua AJ, Rossi HL, Neubert JK (2008) Sex differences in thermal pain sensitivity and sympathetic reactivity for two strains of rat. J Pain 9(8):739–749. https://doi.org/10.1016/j.jpain.2008.03.008

    Article  PubMed  PubMed Central  Google Scholar 

  107. Del Pino J, Martínez MA, Castellano VJ, Ramos E, Martínez-Larrañaga MR, Anadón A (2011) Effects of prenatal and postnatal exposure to amitraz on norepinephrine, serotonin and dopamine levels in brain regions of male and female rats. Toxicology 287(1–3):145–152. https://doi.org/10.1016/j.tox.2011.06.009

    Article  CAS  PubMed  Google Scholar 

  108. González-Pardo H, Arias JI, Gómez-Lázaro E, Taboada IL, Conejo NM (2020) Sex-specific effects of early life stress on brain mitochondrial function, monoamine levels and neuroinflammation. Brain Sci 10(7):447. https://doi.org/10.3390/brainsci10070447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Jankovic M, Spasojevic N, Ferizovic H, Stefanovic B, Dronjak S (2020) Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress. Physiol Behav 227:113174. https://doi.org/10.1016/j.physbeh.2020.113174

    Article  CAS  PubMed  Google Scholar 

  110. Howes LG, Rowe PR, Summers RJ, Louis WJ (1984) Age related changes of catecholamines and their metabolites in central nervous system regions of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (Wky) rats. Clin Exp Hypertens A 6(12):2263–2277. https://doi.org/10.3109/10641968409052207

    Article  CAS  PubMed  Google Scholar 

  111. Vathy I, Katay L (1992) Effects of prenatal morphine on adult sexual behavior and brain catecholamines in rats. Dev Brain Res 68(1):125–131. https://doi.org/10.1016/0165-3806(92)90254-t

    Article  CAS  Google Scholar 

  112. Du X, Yin M, Yuan L, Zhang G, Fan Y, Li Z, Yuan N, Lv X, Zhao X, Zou S, Deng W, Kosten ThR, Zhang XY (2020) Reduction of depression-like behavior in rat model induced by ShRNA targeting norepinephrine transporter in locus coeruleus. Transl Psychiatry 10(1):130. https://doi.org/10.1038/s41398-020-0808-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Waselus M, Galvez JP, Valentino RJ, Van Bockstaele EJ (2006) Differential projections of dorsal raphe nucleus neurons to the lateral septum and striatum. J Cheml Neuroanatomy 31(4):233–242. https://doi.org/10.1016/j.jchemneu.2006.01.007

    Article  CAS  Google Scholar 

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Funding

This work was funded by the Russian Foundation for Basic Research (Grant No. 20-315-90110), to NK, and the State Contract of the Research Institute of General Pathology and Pathophysiology (Registration No. NIOKTR 122022200349-9).

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Authors and Affiliations

  1. Laboratory of General Pathology of the Nervous System, Research Institute of General Pathology and Pathophysiology, 8 Baltiyskaya St, 125315, Moscow, Russian Federation

    Sophie D. Shirenova, Nadezhda N. Khlebnikova & Nataliya A. Krupina

  2. Laboratory of Neurochemical Pharmacology, V. V. Zakusov Research Institute of Pharmacology, 8 Baltiyskaya St, 125315, Moscow, Russian Federation

    Viktor B. Narkevich & Vladimir S. Kudrin

Authors
  1. Sophie D. Shirenova
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  2. Nadezhda N. Khlebnikova
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  3. Viktor B. Narkevich
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  4. Vladimir S. Kudrin
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  5. Nataliya A. Krupina
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Contributions

Conceptualization: NK, SSh; Methodology: SSh, VK; Experimental Data: SSh, NKh, VN, VK, NK; Writing— original draft preparation: SSh, NKh, NK; Writing—review and editing: NK; Supervision: NK. All authors reviewed the manuscript.

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Correspondence to Nataliya A. Krupina.

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The authors declare no competing interests.

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The study was registered with the Ethics Committee of the Institute of General Pathology and Pathophysiology (approval protocol No 3 of 16.06.2020). In accordance with the Rules of Laboratory Practice in the Russian Federation (Order of the Ministry of Health Care and Social Development of the Russian Federation № 199н of 01.04.2016), all procedures were designed to minimize the suffering of the experimental animals.

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Shirenova, S.D., Khlebnikova, N.N., Narkevich, V.B. et al. Nine-month-long Social Isolation Changes the Levels of Monoamines in the Brain Structures of Rats: A Comparative Study of Neurochemistry and Behavior. Neurochem Res 48, 1755–1774 (2023). https://doi.org/10.1007/s11064-023-03858-3

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