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環境因子と神経行動変化に関する分子形態学的研究

Takada, Tadashi 神戸大学

2020.03.25

概要

現代社会において,我々は環境化学物質を含む様々なストレス因子(社会的•物理的•化学的ストレッサー)に曝されており,とくに近年,WHO,米国科学アカデミー,米国小児科学会等,農薬と発達障害との因果関係を示唆する報告が集積されつつある.しかしながら,発症メカニズムとしては,個々の持つ素因に様々なストレスが複合し,閾値を越えた際に症状が顕在化することや,これらの環境要因は組合せにより互いの影響を相加相乗的に強め合う例や不顕性化する例が報告されている.2011年にはWHOが複合曝露評価に対するFrameworkを公表する等,複合的な曝露現状を反映した影響評価の必要性が指摘されている.

1980年代に開発された新規農薬ネオニコチノイド(NN)は,昆虫のニコチン性アセチルコリン受容体(nAChRs)に対して選択的アゴニスト作用を示し,持続的神経興奮を惹起させる.その利便性から,2000年代以降,急速に使用量が増加したが,世界各地で発生した蜂群崩壊症候群の原因物質として指摘され,つい最近では,ウナギやワカサギ激減の要因としてNature誌やScience誌に掲載され,注目を集めた.NNは哺乳類神経細胞のnAChRsに対しても結合能を有し,異常興奮反応を引き起こす[Kimura-Kurodae et al.,2012]とともに,NNの空中散布による「うつ」症状を伴う患者症例が報告された[Taira,2014]ことを端緒に,NNと注意欠如/多動症(AD/HD),うつ病,学習障害との因果関係が問題視され,ヒ卜を含めた脊椎動物に対する不測の影響が懸念されている.このような状況の中で,EUは2013年に予防原則に基づき3種のNNを暫定使用禁止とした一方で,-我が国においてはもともと欧米に比べて規制の緩かった食品中の農薬残留基準値をさらに緩和するという相反した対応がみられ,NNに対する影響評価は国際レベルで急務となっている.これまでに所属研究室では,NNの一種クロチアニジン(CTD)による鳥類および哺乳類の生殖機能障害および神経発達障害に関する報告[Tokumoto et al.,2013;Hoshi et al.,2014; Hirano et al.,2015,2018,2019; Yanai et al.,2017]を行ってきた.そこで本論文では,CTDよりも新しい種類のNNであり,NNのうち国内出荷量が最大であるジノテフラン(DIN)について,哺乳動物への影響を検証する為に,我々が日常的に曝露されている環境化学物質および環境ストレス等の環境要因が生体の神経行動機能に与える影響を多角的に解析し,そのメカニズムを考察した.

第1章では,通常飼育条件下のマウスに対するDINの影響を検証した.ヒトをはじめ動物は,食品(あるいは餌)中に含まれる農薬を日常的に摂取している.「食品を」「日常的に」という点に注目して,「離乳直後の」マウス(C57BL/6N)に「慢性的に」ジノテフランを投与している.pINの最大無作用量550mg/kg/dayを参照し,投与濃度が0,100,500,2,500mg/kg/dayとなるように投与群(DIN-0,DIN-100,DIN-500,DIN-2500)を設定し,自由飲水による投与を行った.神経行動変化の観察には,抗うつ薬の判定指標としてしばしば利用される,尾懸垂試験(TST)および強制水泳試験(FST)を行った後,脳を摘出し背側縫線核におけるセロトニン(5-HT)の発現を免疫組織学的に解析した.その結果,TSTにおいてDINによる不動時間の有意な短縮が認められ,5-HT陽性細胞数では増加傾向が認められた.これらの結果から,農薬評価書に表示されている無作用量以下の短期間投与であっても,通常飼育条件下で幼若期からのマウスが神経行動変化を示すことならびにその作用機序の一端を初めて示すことができた.これらの研究成果の一部について,The Journal of Veterinary Medical Science誌において既に公表している[Takada,et al.,2018].

第Ⅱ章ストレス負荷条件下のマウスに対するDINの影響を第I章同様,無作用量以下で検証した.生後4~8週齢の間,C57BU6N雄マウスに対し6種のストレスのうち1日2種ずつ組み合わせを変えて負荷した.「ストレス負荷マウス」および「非ストレス負荷マウス」に対し,DINの投与濃度が0,500,2,500mg/kg/dayとなるように投与群(DIN-0,DIN-500,DIN-2500)を設定し,自由飲水によるDIN投与を行った.8週齢時に情動変容を調べるオープンフィールド試験(OFT),ならびにTSTおよびFSTを行った後,脳を摘出し正中および背側縫線核における5-HTおよびその合成酵素であるトリプトファンヒドロキシラーゼ2(TPH2),ならびに黒質および腹側被蓋野におけるチロシンヒドロキシラーゼ(TH)の発現を免疫組織学的に解析した.さらに,それぞれのマウスの血液サンプル中のDINおよびコルチコステロンの濃度を測定した.非ストレス負荷マウスでは,DIN投与によってOFTの総移動距離の変化は認められず,DIN-2500におけるTSTの不動時間の減少およびDIN-500におけるFSTの不動時間の増加ならびにDIN-500,DIN-2500における背側縫線核の5-HT発現の増大,DIN-2500における背側縫線核のTPH2発現の増大,DIN-500,DIN-2500における黒質のTH発現の増大が認められた.また,DIN-0のストレス負荷単独曝露マウスではDIN-0の非ストレス負荷マウスと比較して,OFTの総移動距離の増加,TSTにおける不動時間の減少,FSTにおける不動時間の増加,ならびに背側縫線核の5-HTおよびTPH2発現の増大,黒質におけるTH発現の増大が認められた.一方で,ストレス負荷とDINの複合曝露マウスでは,単独曝露マウスト同様に,ストレスマーカーであるコルチコステロン濃度が上昇したにもかかわらず,単独曝露群で認められた変化が打ち消された.以上の結果より,DINは哺乳動物のストレス状態によって異なる影響を与える「神経毒性作用の多面性」ならびにストレスホルモン濃度を上昇させる「内分泌かく乱作用」を有することを初めて示した.これらの研究成果の一部について,The Journal of Veterinary Medical Science誌において既に公表している[Takada,et al.,2020].

以上のように,本研究は「無作用量」という従来の毒性試験から算出された値の安全性•信憑性に一石を投じたものであり,農薬の安全性・リスク評価の上で,現在その評価基準項目から除外されている生体の神経行動学的変化を評価することの重要性を示すものである.加えて,神経作用を有する化学物質の重要な新規エンドポイントを示唆し,今後も生み出され続ける環境化学物質に対する新規リスク評価システムおよびバイオマーカーの開発ならびにヒトを含む動物の保全について重要な知見を与えるものとなる.

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参考文献

Abd-Elhakim, Y. M., Mohammed, H. H. and Mohamed, W. A. M. 2018. Imidacloprid impacts on neurobehavioral performance, oxidative stress, and apoptotic events in the brain of adolescent and adult rats. J. Agric. Food Chem. 66: 13513–13524.

Adell, A., Garcia-Marquez, C., Armario, A. and Gelpi, E. 1988. Chronic stress increases serotonin and noradrenaline in rat brain and sensitizes their responses to a further acute stress. J. Neurochem. 50: 1678–1681.

Altemus, M., Sarvaiya, N. and Neill, E. C. 2014. Sex differences in anxiety and depression clinical perspectives. Front. Neuroendocrinol. 35: 320–330.

Andreasen, J. T. and Redrobe, J. P. 2009. Antidepressant-like effects of nicotine and mecamylamine in the mouse forced swim and tail suspension tests: role of strain, test and sex. Behav. Pharmacol. 20: 286–295.

Andreasen, J. T., Redrobe, J. P. and Nielsen, E. Ø. 2012. Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests: A comparison of SSR180711 and PNU-282987. Pharmacol. Biochem. Behav. 100: 624–629.

Bang, S. J. and Commons, K. G. 2012. Forebrain GABAergic projections from the dorsal raphe nucleus identified by using GAD67-GFP knock-in mice. J. Comp. Neurol. 520: 4157–4167.

Beard, J. D., Umbach, D. M., Hoppin, J. A., Richards, M., Alavanja, M. C., Blair, A., Sandler, D. P. and Kamel, F. 2014. Pesticide exposure and depression among male private pesticide applicators in the agricultural health study. Environ. Health Perspect. 122: 984–991.

Biala, G., Pekala, K., Boguszewska-Czubara, A., Michalak, A., Kruk-Slomka, M. and Budzynska, B. 2017. Behavioral and biochemical interaction between nicotine and chronic unpredictable mild stress in mice. Mol. Neurobiol. 54: 904–921.

Bock, J., Breuer, S., Poeggel, G. and Braun, K. 2017. Early life stress induces attention- deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model. Brain Struct. Funct. 222: 765–780.

Bouchard, M. F., Bellinger, D. C., Wright, R. O. and Weisskopf, M. G. 2010. Attention- deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics 125: e1270–1277.

Burtscher, J., Copin, J. C., Rodrigues, J., Kumar, S. T., Chiki, A., Guillot de Suduiraut, I., Sandi, C. and Lashuel, H. A. 2019. Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology. Neurobiol. Aging 83:11–20.

Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A. and Poulton, R. 2003. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science 301: 386– 389.

Castagné. V., Moser, P., Roux, S. and Porsolt, R. D. 2010. Rodent models of depression: Forced swim and tail suspension behavioral despair tests in rats and mice. Curr. Protoc. Neurosci. Chapter 5: Unit 5. 8.

Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., Beck, S. G. and Berton, O. 2013. Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat. J. Neurosci. 33: 13978–13988.

Coppen, A. 1967. The biochemistry of affective disorders. Br. J. Psychiatry 113: 1237– 1264.

Di Matteo, V., De Blasi, A., Di Giulio, C. and Esposito, E. 2001. Role of 5-HT2C receptors in the control of central dopamine function. Trends Pharmacol. Sci. 22: 229–232.

Dierker, L., Rose, J., Selya, A., Piasecki, T. M., Hedeker, D. and Mermelstein, R. 2015. Depression and nicotine dependence from adolescence to young adulthood. Addict. Behav. 41: 124–128.

Elsabbagh, M., Divan, G., Koh, Y. J., Kim, Y. S., Kauchali, S., Marcín, C., Montiel-Nava, C., Patel, V., Paula, C. S., Wang, C., Yasamy, M. T. and Fombonne, E. 2012. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 5: 160–179.

Faro, L. R., Oliveira, I. M., Durán, R. and Alfonso, M. 2012. In vivo neurochemical characterization of clothianidin induced striatal dopamine release. Toxicology 302: 197–202.

Food Safety Commission of Japan 2016. Agricultural Chemicals and Animal Drug Evaluation Form. 6th ed. pp. 62–64. http://www.fsc.go.jp/fsciis/attachedFile/download?retrievalId=kai20161031no1&fi leId=120 [accessed on January 30, 2020].

Ford, K. A. and Casida, J. E. 2006. Unique and common metabolites of thiamethoxam, clothianidin, and dinotefuran in mice. Chem. Res. Toxicol. 11: 1549–1556.

Garduño, J., Galindo-Charles, L., Jiménez-Rodríguez, J., Galarraga, E., Tapia, D., Mihailescu, S. and Hernandez-Lopez, S. 2012. Presynaptic α4β2 nicotinic acetylcholine receptors increase glutamate release and serotonin neuron excitability in the dorsal raphe nucleus. J. Neurosci. 32: 15148–15157.

GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. 2016. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388: 1545–1602.

Gervais, J. and Rouillard, C. 2000. Dorsal raphe stimulation differentially modulates dopaminergic neurons in the ventral tegmental area and substantia nigra. Synapse 35: 281–291.

Gill, R. J., Ramos-Rodriguez, O. and Raine, N. E. 2012. Combined pesticide exposure severely affects individual- and colony-level traits in bees. Nature 491: 105–108.

Goesling, J., Brummett, C. M., Meraj, T. S., Moser, S. E., Hassett, A. L. and Ditre, J. W. 2015. Associations between pain, current tobacco smoking, depression, and fibromyalgia status among treatment-seeking chronic pain patients. Pain Med. 16: 1433–1442.

Graeff, F. G., Viana, M. B. and Mora, P. O. 1997. Dual role of 5-HT in defense and anxiety.Neurosci. Biobehav. Rev. 21:791–799.

Grønli, J., Murison, R., Fiske, E., Bjorvatn, B., Sørensen, E., Portas, C. M. and Ursin, R. 2005. Effects of chronic mild stress on sexual behavior, locomotor activity and consumption of sucrose and saccharine solutions. Physiol. Behav. 31: 571–577.

Guimarães, F. S., Del Bel, E. A., Padovan, C. M., Netto, S. M. and de Almeida, R. T. 1993. Hippocampal 5-HT receptors and consolidation of stressful memories. Behav. Brain Res. 58: 133–139.

Hagino, Y., Kasai, S., Fujita, M., Setogawa, S., Yamaura, H., Yanagihara, D., Hashimoto, M., Kobayashi, K., Meltzer, H. Y. and Ikeda, K. 2015. Involvement of cholinergic system in hyperactivity in dopamine-deficient mice. Neuropsychopharmacology 40: 1141–1150.

Hallmann, C. A., Foppen, R. P., van Turnhout, C. A., de Kroon, H. and Jongejans, E. 2014. Declines in insectivorous birds are associated with high neonicotinoid concentrations. Nature 511: 341–343.

Henry, M., Béguin, M., Requier, F., Rollin, O., Odoux, J. F., Aupinel, P., Aptel, J., Tchamitchian, S. and Decourtye, A. 2012. A common pesticide decreases foraging success and survival in honey bees. Science 336: 348–350.

Hirano, T., Yanai, S., Omotehara, T., Hashimoto, R., Umemura, Y., Kubota, N., Minami, K., Nagahara, D., Matsuo, E., Aihara, Y., Shinohara, R., Furuyashiki, T., Mantani, Y., Yokoyama, T., Kitagawa, H. and Hoshi, N. 2015. The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice. J. Vet. Med. Sci. 77: 1207–1215.

Hirano, T., Yanai, S., Takada, T., Yoneda, N., Omotehara, T., Kubota, N., Minami, K., Yamamoto, A., Mantani, Y., Yokoyama, T., Kitagawa, H. and Hoshi, N. 2018. NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety- related behavior with human-audible vocalizations in male mice in a novel environment. Toxicol. Lett. 282: 57–63.

Hiremagalur, B., Nankova, B., Nitahara, J., Zeman, R. and Sabban, E. L. 1993. Nicotine increases expression of tyrosine hydroxylase gene. Involvement of protein kinase A- mediated pathway. J. Biol. Chem. 268: 23704–23711.

Hoshi, N., Hirano, T., Omotehara, T., Tokumoto, J., Umemura, Y., Mantani, Y., Tanida, T., Warita, K., Tabuchi, Y., Yokoyama, T. and Kitagawa, H. 2014. Insight into the mechanism of reproductive dysfunction caused by neonicotinoid pesticides. Biol. Pharm. Bull. 37: 1439–1443.

Hunter, R. G., Bloss, E. B., McCarthy, K. J. and McEwen, B. S. 2010. Regulation of the nicotinic receptor alpha7 subunit by chronic stress and corticosteroids. Brain Res. 1325: 141–146.

Ikemoto, K., Nishimura, A., Okado, N., Mikuni, M., Nishi, K. and Nagatsu, I. 2000. Human midbrain dopamine neurons express serotonin 2A receptor: an immunohistochemical demonstration. Brain Res. 853: 377–380.

Jang, M. H., Shin, M. C., Lee, T. H., Kim, Y. P., Jung, S. B., Shin, D. H., Kim, H., Kim,S. S., Kim, E. H. and Kim, C. J. 2002. Alcohol and nicotine administration inhibits serotonin synthesis and tryptophan hydroxylase expression in dorsal and median raphe of young rats. Neurosci. Lett. 329: 141–144.

Kenny, P. J., File, S. E. and Rattray, M. 2001. Nicotine regulates 5-HT1A receptor gene expression in the cerebral cortex and dorsal hippocampus. Eur. J. Neurosci. 13: 1267–1271.

Kimura-Kuroda, J., Komuta, Y., Kuroda, Y., Hayashi, M. and Kawano, H. 2012. Nicotine- like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from neonatal rats. PLoS ONE 7: e32432.

Lazarus, R. S. 1993. From psychological stress to the emotions: a history of changing outlooks. Annu. Rev. Psychol. 44:1–21.

Leonard, S., Gault, J., Hopkins, J., Logel, J., Vianzon, R., Short, M., Drebing, C., Berger, R., Venn, D., Sirota, P., Zerbe, G., Olincy, A., Ross, R. G., Adler, L. E. and Freedman,R. 2002. Association of promoter variants in the α7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia. Arch. Gen. Psychiatry 59: 1085–1096.

Mahar, I., Bambico, F. R., Mechawar, N. and Nobrega, J. N. 2014. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci. Biobehav. Rev. 38: 173–192.

Meyer, A., Koifman, S., Koifman, R. J., Moreira, J. C., de Rezende, Chrisman, J. and Abreu-Villaca, Y. 2010. Mood disorders hospitalizations, suicide attempts, and suicide mortality among agricultural workers and residents in an area with intensive use of pesticides in Brazil. J. Toxicol. Environ. Health A. 73: 866–877.

Mineur, Y. S. and Picciotto, M. R. 2010. Nicotine receptors and depression: Revisiting and revising the cholinergic hypothesis. Trends Pharmacol. Sci. 31: 580–586.

Mineur, Y. S., Einstein, E. B., Bentham, M. P., Wigestrand, M. B., Blakeman, S., Newbold,S. A. and Picciotto, M. R. 2015. Expression of the 5-HT1A serotonin receptor in the hippocampus is required for social stress resilience and the antidepressant-like effects induced by the nicotinic partial agonist cytisine. Neuropsychopharmacology 40: 938–946.

Mineur, Y. S., Fote, G. M., Blakeman, S., Cahuzac, E. L., Newbold, S. A. and Picciotto,M. R. 2016. Multiple nicotinic acetylcholine receptor subtypes in the mouse amygdala regulate affective behaviors and response to social stress. Neuropsychopharmacology 41: 1579–1587.

Ministry of Education, Culture, Sports, Science and Technology. 2017. Results of the survey on the status of guidance by special needs education. (https://www.mext.go.jp/a_menu/shotou/tokubetu/ icsFiles/afieldfile/2018/05/14/ 1402845_03.pdf) [accessed on January 30, 2020].

Ministry of Health, Labour and Welfare. 2017. Patient Survey. (https://www.mhlw.go.jp/toukei/saikin/hw/kanja/17/dl/kanja.pdf) [accessed on January 30, 2020].

Morel, C., Fernandez, S. P., Pantouli, F., Meye, F. J., Marti, F., Tolu, S., Parnaudeau, S., Marie, H., Tronche, F., Maskos, U., Moretti, M., Gotti, C., Han, M-H., Bailey, A., Mameli, M., Barik, J. and Faure, P. 2018. Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity. Mol. Psychiatry 23: 1597–1605.

Ochoa, E. L. M., Chattopadhyay, A. and McNamee, M. G. 1989. Desensitization of the nicotinic acetylcholine receptor: Molecular mechanisms and effect of modulators. Cell. Mol. Neurobiol. 9: 141–178.

Owens, M. J. and Nemeroff, C. B. 1994. Role of serotonin in the pathophysiology of depression: Focus on the serotonin transporter. Clin. Chem. 40: 288–295.

Paxinos, G. and Franklin, K. B. J. 2001. The Mouse Brain in Stereotaxic Coordinates, 2nd ed., Academic Press, Hong Kong.Picciotto, M. R., Addy, N. A., Mineur, Y. S. and Brunzell, D. H. 2008. It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Prog. Neurobiol. 84: 329–342.

Picciotto, M. R., Lewis, A. S., van Schalkwyk, G. I. and Mineur, Y. S. 2015. Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states. Neuropharmacology 96: 235–243.

Porsolt, R. D., Bertin, A. and Jalfre, M. 1977. Behavioral despair in mice: a primary screening test for antidepressants. Arch. Int. Pharmacodyn. Ther. 229: 327–336.

Renard, C. E., Dailly, E., David, D. J. P., Hascoet, M. and Bourin, M. 2003. Monoamine metabolism changes following the mouse forced swimming test but not the tail suspension test. Fundam. Clin. Pharmacol. 17: 449–455.

Roberts, J. R., Karr, C. J. and Council on Environmental Health. 2012. Pesticide exposure in children. Pediatrics 130: e1765–1788.

Rodrigues, K. J. A., Santana, M. B., Do Nascimento, J. L. M., Picanço-Diniz, D. L. W., Maués, L. A. L., Santos, S. N., Ferreira, V. M. M., Alfonso, M., Durán, R. and Faro,L. R. F. 2010. Behavioral and biochemical effects of neonicotinoid thiamethoxam on the cholinergic system in rats. Ecotoxicol. Environ. Saf. 73: 101–107.

Sealey, L. A., Hughes, B. W., Sriskanda, A. N., Guest, J. R., Gibson, A. D., Johnson- Williams, L., Pace, D. G. and Bagasra, O. 2016. Environmental factors in the development of autism spectrum disorders. Environ. Int. 88: 288–298.

Steru, L., Chermat, R., Thierry, B. and Simon, P. 1985. The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology 85: 367–370.

Steru, L., Chermat, R., Thierry, B., Mico, J. A., Lenegre, A., Steru, M., Simon, P. and Porsolt, R.D. 1987. The automated tail suspension test: A computerized device which differentiates psychotropic drugs. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 11: 659–671.

Strachan, E., Duncan, G., Horn, E. and Turkheimer, E. 2017. Neighborhood deprivation and depression in adult twins: genetics and gene×environment interaction. Psychol. Med. 47: 627–638.

Sugama, S. and Kakinuma, Y. 2016. Loss of dopaminergic neurons occurs in the ventral tegmental area and hypothalamus of rats following chronic stress: Possible pathogenetic loci for depression involved in Parkinson’s disease. Neurosci. Res. 111: 48–55.

Taira, K. 2014. Human neonicotinoids exposure in Japan. Jpn. J. Clin. Ecol. 23: 14–24. Takada, T., Yoneda, N., Hirano, T., Yanai, S., Yamamoto, A., Mantani, Y., Yokoyama, T.,Kitagawa, H., Tabuchi, Y. and Hoshi, N. 2018. Verification of the causal relationship between subchronic exposures to dinotefuran and depression-related phenotype in juvenile mice. J. Vet. Med. Sci. 80: 720–724.

Tanida, T., Warita, K., Ishihara, K., Fukui, S., Mitsuhashi, T., Sugawara, T., Tabuchi, Y., Nanmori, T., Qi, W. M., Inamoto, T., Yokoyama, T., Kitagawa, H. and Hoshi N. 2009. Fetal and neonatal exposure to three typical environmental chemicals with different mechanisms of action: Mixed exposure to phenol, phthalate, and dioxin cancels the effects of sole exposure on mouse midbrain dopaminergic nuclei. Toxicol. Lett. 189: 40–47.

Tizabi, Y., Overstreet, D.H., Rezvani, A. H., Louis, V. A., Clark Jr., E., Janowsky, D. S. and Kling, M. A., 1999. Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology 142: 193–199.

Tokumoto, J., Danjo, M., Kobayashi, Y., Kinoshita, K., Omotehara, T., Tatsumi, A., Hashiguchi, M., Sekijima, T., Kamisoyama, H., Yokoyama, T., Kitagawa, H. and Hoshi, N. 2013 Effects of exposure to clothianidin on the reproductive system of male quails. J. Vet. Med. Sci. 75: 755–760.

Ueyama, J., Harada, K. H., Koizumi, A., Sugiura, Y., Kondo, T., Saito, I. and Kamijima,M. 2015. Temporal levels of urinary neonicotinoid and dialkylphosphate concentrations in Japanese women between 1994 and 2011. Environ. Sci. Technol. 49: 14522–14528.

Vázquez-Palacios, G., Bonilla-Jaime, H. and Velázquez-Moctezuma, J. 2004. Antidepressant-like effects of the acute and chronic administration of nicotine in the rat forced swimming test and its interaction with flouxetine. Pharmacol. Biochem. Behav. 78: 165–169.

Whitehorn, P. R., O’Connor, S., Wackers, F. L. and Goulson, D. 2012. Neonicotinoid pesticide reduces bumble bee colony growth and queen production. Science 336: 351–352.

Willner, P., Towell, A., Sampson, D., Sophokleous, S. and Muscat, R. 1987. Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93: 358–364.

Winders, S. E., Grunberg, N. E., Benowitz, N. L. and Alvares, A. P. 1998. Effects of stress on circulating nicotine and cotinine levels and in vitro nicotine metabolism in the rat. Psychopharmacology 137: 383–390.

World Health Organization (WHO) and United Nations Environment Programme (UNEP) 2012. State of the Science of Endocrine Disrupting Chemicals 2012, an assessment of the state of the science of endocrine disruptors prepared by a group of experts for the UNEP and WHO. (Bergman, Å., Heindel, J. J., Jobling, S., Kidd, K. A. and Zoeller, R. T. eds.), UNEP: Nairobi, Kenya; WHO: Geneva, Switzerland.

Xu, Z., Seidler, F. J., Cousins, M. M., Slikker Jr., W. and Slotkin, T. A. 2002. Adolescent nicotine administration alters serotonin receptors and cell signaling mediated through adenylyl cyclase. Brain Res. 951: 280–292.

Yamamuro, M., Komuro, T., Kamiya, H., Kato, T., Hasegawa, H. and Kameda, Y. 2019. Neonicotinoids disrupt aquatic food webs and decrease fishery yields. Science 366: 620–623.

Yanai, S., Hirano, T., Omotehara, T., Takada, T., Yoneda, N., Kubota, N., Yamamoto, A., Mantani, Y., Yokoyama, T., Kitagawa, H. and Hoshi, N. 2017. Prenatal and early postnatal NOAEL-dose clothianidin exposure leads to a reduction of germ cells in juvenile male mice. J. Vet. Med. Sci. 79: 1196–1203.

Yoneda, N., Takada, T., Hirano, T., Yanai, S., Yamamoto, A., Mantani, Y., Yokoyama, T., Kitagawa, H., Tabuchi, Y. and Hoshi, N. 2018. Peripubertal exposure to the neonicotinoid pesticide dinotefuran affects dopaminergic neurons and causes hyperactivity in male mice. J. Vet. Med. Sci. 80: 634–637.

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