DOI QR코드

DOI QR Code

Toluene Inhalation Causes Early Anxiety and Delayed Depression with Regulation of Dopamine Turnover, 5-HT1A Receptor, and Adult Neurogenesis in Mice

  • Kim, Jinhee (College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University) ;
  • Lim, Juhee (College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University) ;
  • Moon, Seong-Hee (College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University) ;
  • Liu, Kwang-Hyeon (BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Choi, Hyun Jin (College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University)
  • Received : 2020.04.08
  • Accepted : 2020.04.16
  • Published : 2020.05.01

Abstract

Inhaled solvents such as toluene are of particular concern due to their abuse potential that is easily exposed to the environment. The inhalation of toluene causes various behavioral problems, but, the effect of short-term exposure of toluene on changes in emotional behaviors over time after exposure and the accompanying pathological characteristics have not been fully identified. Here, we evaluated the behavioral and neurochemical changes observed over time in mice that inhaled toluene. The mice were exposed to toluene for 30 min at a concentration of either 500 or 2,000 ppm. Toluene did not cause social or motor dysfunction in mice. However, increased anxiety-like behavior was detected in the short-term after exposure, and depression-like behavior appeared as delayed effects. The amount of striatal dopamine metabolites was significantly decreased by toluene, which continued to be seen for up to almost two weeks after inhalation. Additionally, an upregulation of serotonin 1A (5-HT1A) receptor in the hippocampus and the substantia nigra, as well as reduced immunoreactivity of neurogenesis markers in the dentate gyrus, was observed in the mice after two weeks. These results suggest that toluene inhalation, even single exposure, mimics early anxiety-and delayed depression-like emotional disturbances, underpinned by pathological changes in the brain.

Keywords

References

  1. Albert, P. R., Le Francois, B. and Millar, A. M. (2011) Transcriptional dysregulation of 5-HT1A autoreceptors in mental illness. Mol. Brain 4, 21. https://doi.org/10.1186/1756-6606-4-21
  2. Apawu, A. K., Mathews, T. A. and Bowen, S. E. (2015) Striatal dopamine dynamics in mice following acute and repeated toluene exposure. Psychopharmacology (Berl.) 232, 173-184. https://doi.org/10.1007/s00213-014-3651-x
  3. Arnold, G. L., Kirby, R. S., Langendoerfer, S. and Wilkins-Haug, L. (1994) Toluene embryopathy: clinical delineation and developmental follow-up. Pediatrics 93, 216-220.
  4. Arrant, A. E., Schramm-Sapyta, N. L. and Kuhn, C. M. (2013) Use of the light/dark test for anxiety in adult and adolescent male rats. Behav. Brain Res. 256, 119-127. https://doi.org/10.1016/j.bbr.2013.05.035
  5. Beasley, T. E., Evansky, P. A., Gilbert, M. E. and Bushnell, P. J. (2010) Behavioral effects of subchronic inhalation of toluene in adult rats. Neurotoxicol. Teratol. 32, 611-619. https://doi.org/10.1016/j.ntt.2010.05.005
  6. Beckley, J. T. and Woodward, J. J. (2011) The abused inhalant toluene differentially modulates excitatory and inhibitory synaptic transmission in deep-layer neurons of the medial prefrontal cortex. Neuropsychopharmacology 36, 1531-1542. https://doi.org/10.1038/npp.2011.38
  7. Boldrini, M., Underwood, M. D., Mann, J. J. and Arango, V. (2008) Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides. J. Psychiatr. Res. 42, 433-442. https://doi.org/10.1016/j.jpsychires.2007.05.004
  8. Bowen, S. E., Hannigan, J. H., Davidson, C. J. and Callan, S. P. (2018) Abstinence following toluene exposure increases anxiety-like behavior in mice. Neurotoxicol. Teratol. 65, 42-50. https://doi.org/10.1016/j.ntt.2017.12.010
  9. Chiavegatto, S., Izidio, G. S., Mendes-Lana, A., Aneas, I., Freitas, T. A., Torrao, A. S., Conceicao, I. M., Britto, L. R. and Ramos, A. (2009) Expression of alpha-synuclein is increased in the hippocampus of rats with high levels of innate anxiety. Mol. Psychiatry 14, 894-905. https://doi.org/10.1038/mp.2008.43
  10. Crawley, J. and Goodwin, F. K. (1980) Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav. 13, 167-170. https://doi.org/10.1016/0091-3057(80)90067-2
  11. Cruz, S. L., Rivera-Garcia, M. T. and Woodward, J. J. (2014) Review of toluene action: clinical evidence, animal studies and molecular targets. J. Drug Alcohol Res. 3, 235840.
  12. Cruz, S. L., Soberanes-Chavez, P., Paez-Martinez, N. and Lopez-Rubalcava, C. (2009) Toluene has antidepressant-like actions in two animal models used for the screening of antidepressant drugs. Psychopharmacology (Berl.) 204, 279-286. https://doi.org/10.1007/s00213-009-1462-2
  13. Dale, E., Pehrson, A. L., Jeyarajah, T., Li, Y., Leiser, S. C., Smagin, G., Olsen, C. K. and Sanchez, C. (2016) Effects of serotonin in the hippocampus: how SSRIs and multimodal antidepressants might regulate pyramidal cell function. CNS Spectr. 21, 143-161. https://doi.org/10.1017/s1092852915000425
  14. Djavadian, R. L. (2004) Serotonin and neurogenesis in the hippocampal dentate gyrus of adult mammals. Acta Neurobiol. Exp. (Wars.) 64, 189-200.
  15. Erro, R., Pappata, S., Amboni, M., Vicidomini, C., Longo, K., Santangelo, G., Picillo, M., Vitale, C., Moccia, M., Giordano, F., Brunetti, A., Pellecchia, M. T., Salvatore, M. and Barone, P. (2012) Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson's disease patients. Parkinsonism Relat. Disord. 18, 1034-1038. https://doi.org/10.1016/j.parkreldis.2012.05.022
  16. Felix-Ortiz, A. C. and Tye, K. M. (2014) Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. J. Neurosci. 34, 586-595. https://doi.org/10.1523/JNEUROSCI.4257-13.2014
  17. Gerasimov, M. R., Schiffer, W. K., Marstellar, D., Ferrieri, R., Alexoff, D. and Dewey, S. L. (2002) Toluene inhalation produces regionally specific changes in extracellular dopamine. Drug Alcohol Depend. 65, 243-251. https://doi.org/10.1016/S0376-8716(01)00166-1
  18. Gmaz, J. M., Matthews, B. A. and McKay, B. E. (2012) Toluene inhalation modulates dentate gyrus granule cell output in vivo. Neurotoxicol. Teratol. 34, 403-412. https://doi.org/10.1016/j.ntt.2012.04.011
  19. Gospe, S. M., Jr. and Zhou, S. S. (2000) Prenatal exposure to toluene results in abnormal neurogenesis and migration in rat somatosensory cortex. Pediatr. Res. 47, 362-368. https://doi.org/10.1203/00006450-200003000-00013
  20. Han, A., Yeo, H., Park, M. J., Kim, S. H., Choi, H. J., Hong, C. W. and Kwon, M. S. (2015) IL-4/10 prevents stress vulnerability following imipramine discontinuation. J. Neuroinflammation 12, 197. https://doi.org/10.1186/s12974-015-0416-3
  21. Howard, M. O., Bowen, S. E., Garland, E. L., Perron, B. E. and Vaughn, M. G. (2011) Inhalant use and inhalant use disorders in the United States. Addict. Sci. Clin. Pract. 6, 18-31.
  22. Lee, Y. L., Pai, M. C., Chen, J. H. and Guo, Y. L. (2003) Central neurological abnormalities and multiple chemical sensitivity caused by chronic toluene exposure. Occup. Med. (Lond.) 53, 479-482. https://doi.org/10.1093/occmed/kqg095
  23. Lim, J., Bang, Y. and Choi, H. J. (2018a) Abnormal hippocampal neurogenesis in Parkinson's disease: relevance to a new therapeutic target for depression with Parkinson's disease. Arch. Pharm. Res. 41, 943-954. https://doi.org/10.1007/s12272-018-1063-x
  24. Lim, J., Bang, Y., Choi, J. H., Han, A., Kwon, M. S., Liu, K. H. and Choi, H. J. (2018b) LRRK2 G2019S induces anxiety/depression-like behavior before the onset of motor dysfunction with 5-HT1A receptor upregulation in mice. J. Neurosci. 38, 1611-1621. https://doi.org/10.1523/JNEUROSCI.4051-15.2017
  25. Lin, B. F., Ou, M. C., Chung, S. S., Pang, C. Y. and Chen, H. H. (2010) Adolescent toluene exposure produces enduring social and cognitive deficits in mice: an animal model of solvent-induced psychosis. World J. Biol. Psychiatry 11, 792-802. https://doi.org/10.3109/15622970903406234
  26. Lopez-Rubalcava, C., Hen, R. and Cruz, S. L. (2000) Anxiolytic-like actions of toluene in the burying behavior and plus-maze tests: differences in sensitivity between 5-HT(1B) knockout and wild-type mice. Behav. Brain Res. 115, 85-94. https://doi.org/10.1016/S0166-4328(00)00241-2
  27. Marjot, R. and McLeod, A. A. (1989) Chronic non-neurological toxicity from volatile substance abuse. Hum. Toxicol. 8, 301-306. https://doi.org/10.1177/096032718900800408
  28. Paez-Martinez, N., Cruz, S. L. and Lopez-Rubalcava, C. (2003) Comparative study of the effects of toluene, benzene, 1,1,1-trichloroethane, diethyl ether, and flurothyl on anxiety and nociception in mice. Toxicol. Appl. Pharmacol. 193, 9-16. https://doi.org/10.1016/S0041-008X(03)00335-1
  29. Pineyro, G. and Blier, P. (1999) Autoregulation of serotonin neurons: role in antidepressant drug action. Pharmacol. Rev. 51, 533-591.
  30. Przegalinski, E. and Filip, M. (1997) Stimulation of serotonin (5-HT)1A receptors attenuates the locomotor, but not the discriminative, effects of amphetamine and cocaine in rats. Behav. Pharmacol. 8, 699-706. https://doi.org/10.1097/00008877-199712000-00004
  31. Pyykko, K., Tahti, H. and Vapaatalo, H. (1977) Toluene concentrations in various tissues of rats after inhalation and oral administration. Arch. Toxicol. 38, 169-176. https://doi.org/10.1007/BF00293651
  32. Riegel, A. C., Zapata, A., Shippenberg, T. S. and French, E. D. (2007) The abused inhalant toluene increases dopamine release in the nucleus accumbens by directly stimulating ventral tegmental area neurons. Neuropsychopharmacology 32, 1558-1569. https://doi.org/10.1038/sj.npp.1301273
  33. Salmanzadeh, H., Ahmadi-Soleimani, S. M., Pachenari, N., Azadi, M., Halliwell, R. F., Rubino, T. and Azizi, H. (2020) Adolescent drug exposure: a review of evidence for the development of persistent changes in brain function. Brain Res. Bull. 156, 105-117. https://doi.org/10.1016/j.brainresbull.2020.01.007
  34. Schoenfeld, T. J. and Cameron, H. A. (2015) Adult neurogenesis and mental illness. Neuropsychopharmacology 40, 113-128. https://doi.org/10.1038/npp.2014.230
  35. Seo, H. S., Yang, M., Song, M. S., Kim, J. S., Kim, S. H., Kim, J. C., Kim, H., Shin, T., Wang, H. and Moon, C. (2010) Toluene inhibits hippocampal neurogenesis in adult mice. Pharmacol. Biochem. Behav. 94, 588-594. https://doi.org/10.1016/j.pbb.2009.11.015
  36. Siopi, E., Denizet, M., Gabellec, M. M., de Chaumont, F., Olivo-Marin, J. C., Guilloux, J. P., Lledo, P. M. and Lazarini, F. (2016) Anxietyand depression-like states lead to pronounced olfactory deficits and impaired adult neurogenesis in mice. J. Neurosci. 36, 518-531. https://doi.org/10.1523/JNEUROSCI.2817-15.2016
  37. Stengard, K., Hoglund, G. and Ungerstedt, U. (1994) Extracellular dopamine levels within the striatum increase during inhalation exposure to toluene: a microdialysis study in awake, freely moving rats. Toxicol. Lett. 71, 245-255. https://doi.org/10.1016/0378-4274(94)90111-2
  38. Stockmeier, C. A., Shapiro, L. A., Dilley, G. E., Kolli, T. N., Friedman, L. and Rajkowska, G. (1998) Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J. Neurosci. 18, 7394-7401. https://doi.org/10.1523/jneurosci.18-18-07394.1998
  39. Tas, U., Ekici, F., Koc, F., Sogut, E., Ayan, M., Kuloglu, T., Arici, A. and Ozyurt, B. (2013) Acute cardiotoxic effects of high dose toluene: an experimental study. Anadolu Kardiyol. Derg. 13, 3-8.
  40. Terzian, A. L., Drago, F., Wotjak, C. T. and Micale, V. (2011) The dopamine and cannabinoid interaction in the modulation of emotions and cognition: assessing the role of cannabinoid CB1 receptor in neurons expressing dopamine D1 receptors. Front. Behav. Neurosci. 5, 49. https://doi.org/10.3389/fnbeh.2011.00049
  41. Thiemann, G., Watt, C. A., Ledent, C., Molleman, A. and Hasenohrl, R. U. (2009) Modulation of anxiety by acute blockade and genetic deletion of the CB(1) cannabinoid receptor in mice together with biogenic amine changes in the forebrain. Behav. Brain Res. 200, 60-67. https://doi.org/10.1016/j.bbr.2008.12.035
  42. Tianzhu, Z., Shihai, Y. and Juan, D. (2014) Antidepressant-like effects of cordycepin in a mice model of chronic unpredictable mild stress. Evid. Based Complement. Alternat. Med. 2014, 438506.
  43. Yamamura, S., Abe, M., Nakagawa, M., Ochi, S., Ueno, S. and Okada, M. (2011) Different actions for acute and chronic administration of mirtazapine on serotonergic transmission associated with raphe nuclei and their innervation cortical regions. Neuropharmacology 60, 550-560. https://doi.org/10.1016/j.neuropharm.2010.12.025
  44. Yang, M., Kim, S. H., Kim, J. C., Shin, T. and Moon, C. (2010) Toluene induces depression-like behaviors in adult mice. Toxicol. Res. 26, 315-320. https://doi.org/10.5487/TR.2010.26.4.315
  45. Yankelevitch-Yahav, R., Franko, M., Huly, A. and Doron, R. (2015) The forced swim test as a model of depressive-like behavior. J. Vis. Exp. (97), 52587.
  46. Yau, S. Y., Lau, B. W., Tong, J. B., Wong, R., Ching, Y. P., Qiu, G., Tang, S. W., Lee, T. M. and So, K. F. (2011) Hippocampal neurogenesis and dendritic plasticity support running-improved spatial learning and depression-like behaviour in stressed rats. PLoS ONE 6, e24263. https://doi.org/10.1371/journal.pone.0024263
  47. Yoon, J. H., Seo, H. S., Lee, J., Moon, C. and Lee, K. (2016) Acute high-level toluene exposure decreases hippocampal neurogenesis in rats. Toxicol. Ind. Health 32, 1910-1920. https://doi.org/10.1177/0748233715599087
  48. Zachrison, L., Ruchkin, V., Stickley, A. and Koposov, R. (2017) Inhalant use and mental health problems in russian juvenile delinquents. Subst. Use Misuse 52, 1616-1623. https://doi.org/10.1080/10826084.2017.1293106
  49. Zarrindast, M. R. and Khakpai, F. (2015) The modulatory role of dopamine in anxiety-like behavior. Arch. Iran. Med. 18, 591-603.
  50. Zhvania, M. G., Chilachava, L. R., Japaridze, N. J., Gelazonia, L. K. and Lordkipanidze, T. G. (2012) Immediate and persisting effect of toluene chronic exposure on hippocampal cell loss in adolescent and adult rats. Brain Res. Bull. 87, 187-192. https://doi.org/10.1016/j.brainresbull.2011.10.021