Skip to main content
Log in

Mother/Offspring Co-administration of the Traditional Herbal Remedy Yokukansan During the Nursing Period Influences Grooming and Cerebellar Serotonin Levels in a Rat Model of Neurodevelopmental Disorders

  • Original Paper
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Neurodevelopmental impairment in the serotonergic system may be involved in autism spectrum disorder. Yokukansan is a traditional herbal remedy for restlessness and agitation in children, and mother–infant co-administration (MICA) to both the child and the nursing mother is one of the recommended treatment approaches. Recent studies have revealed the neuropharmacological properties of Yokukansan (YKS), including its 5-HT1A (serotonin) receptor agonistic effects. We investigated the influence of YKS treatment on behavior in a novel environment and on brain monoamine metabolism during the nursing period in an animal model of neurodevelopmental disorders, prenatally BrdU (5-bromo-2′-deoxyuridine)-treated rats (BrdU-rats). YKS treatment did not influence locomotor activity in BrdU-rats but reduced grooming in open-field tests. YKS treatment without MICA disrupted the correlation between locomotor behaviors and rearing and altered levels of serotonin and its metabolite in the cerebellum. These effects were not observed in the group receiving YKS treatment with MICA. These data indicate a direct pharmacological effect of YKS on the development of grooming behavior and profound effects on cerebellar serotonin metabolism, which is thought to be influenced by nursing conditions.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Croonenberghs J, Delmeire L, Verkerk R, Lin AH, Meskal A, Neels H, et al. Peripheral markers of serotonergic and noradrenergic function in post-pubertal, Caucasian males with autistic disorder. Neuropsychopharmacology. 2000;22(3):275–83.

    Article  CAS  PubMed  Google Scholar 

  2. Croonenberghs J, Verkerk R, Scharpe S, Deboutte D, Maes M. Serotonergic disturbances in autistic disorder: L-5-hydroxytryptophan administration to autistic youngsters increases the blood concentrations of serotonin in patients but not in controls. Life Sci. 2005;76(19):2171–83.

    Article  CAS  PubMed  Google Scholar 

  3. Hollander E, Novotny S, Allen A, Aronowitz B, Cartwright C, DeCaria C. The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder. Neuropsychopharmacology. 2000;22(2):163–7.

    Article  CAS  PubMed  Google Scholar 

  4. Makkonen I, Riikonen R, Kokki H, Airaksinen MM, Kuikka JT. Serotonin and dopamine transporter binding in children with autism determined by SPECT. Dev Med Child Neurol. 2008;50(8):593–7.

    Article  PubMed  Google Scholar 

  5. Oblak A, Gibbs TT, Blatt GJ. Reduced Serotonin Receptor Subtypes in a Limbic and a Neocortical Region in Autism. Autism Res. 2013;6(6):571–83.

    Article  PubMed  Google Scholar 

  6. Goldberg J, Anderson GM, Zwaigenbaum L, Hall GB, Nahmias C, Thompson A, et al. Cortical serotonin type-2 receptor density in parents of children with autism spectrum disorders. J Autism Dev Disord. 2009;39(1):97–104.

    Article  PubMed  Google Scholar 

  7. Carrasco M, Volkmar FR, Bloch MH. Pharmacologic treatment of repetitive behaviors in autism spectrum disorders: evidence of publication bias. Pediatrics. 2013;129(5):e1301–10.

    Article  Google Scholar 

  8. Hollander E, Soorya L, Chaplin W, Anagnostou E, Taylor BP, Ferretti CJ, et al. A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. Am J Psychiatry. 2012;169(3):292–9.

    Article  PubMed  Google Scholar 

  9. Pardo CA, Eberhart CG. The neurobiology of autism. Brain Pathol. 2007;17(4):434–47.

    Article  CAS  PubMed  Google Scholar 

  10. Boccuto L, Chen CF, Pittman AR, Skinner CD, McCartney HJ, Jones K, et al. Decreased tryptophan metabolism in patients with autism spectrum disorders. Mol Autism. 2013;4(1):16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Cook Jr EH, Charak DA, Arida J, Spohn JA, Roizen NJ, Leventhal BL. Depressive and obsessive-compulsive symptoms in hyperserotonemic parents of children with autistic disorder. Psychiatry Res. 1994;52(1):25–33.

    Article  PubMed  Google Scholar 

  12. Sundström E, Kölare S, Souverbie F, Samuelsson EB, Pschera H, Lunell NO, et al. Neurochemical differentiation of human bulbospinal monoaminergic neurons during the first trimester. Brain Res Dev Brain Res. 1993;75(1):1–12.

    Article  PubMed  Google Scholar 

  13. Chugani DC, Muzik O, Behen M, Rothermel R, Janisse JJ, Lee J, et al. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol. 1999;45(3):287–95.

    Article  CAS  PubMed  Google Scholar 

  14. Kane MJ, Angoa-Perez M, Briggs DI, Sykes CE, Francescutti DM, Rosenberg DR, et al. Mice genetically depleted of brain serotonin display social impairments, communication deficits and repetitive behaviors: possible relevance to autism. PLoS One. 2012;7(11):e48975.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Miyaoka T, Horigichi J. Clinical Potential of Yi-Gan San (Yokukansan) for the Treatment of Psychiatric Disorders. Curr Psychiatr Rev. 2009;5(4):271–5.

    Article  Google Scholar 

  16. Terasawa K. KAMPO, Japanese-oriental medicine Insights from clinical cases. Tokyo: K.K. Standard McIntyre; 1993.

    Google Scholar 

  17. Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N, et al. A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry. 2005;66(2):248–52.

    Article  PubMed  Google Scholar 

  18. Mizukami K, Asada T, Kinoshita T, Tanaka K, Sonohara K, Nakai R, et al. A randomized cross-over study of a traditional Japanese medicine (kampo), Yokukansan, in the treatment of the behavioural and psychological symptoms of dementia. Int J Neuropsychopharmacol. 2009;12(2):191–9.

    Article  CAS  PubMed  Google Scholar 

  19. Okahara K, Ishida Y, Hayashi Y, Inoue T, Tsuruta K, Takeuchi K, et al. Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(3):532–6.

    Article  CAS  PubMed  Google Scholar 

  20. Shinno H, Utani E, Okazaki S, Kawamukai T, Yasuda H, Inagaki T, et al. Successful treatment with Yi-Gan San for psychosis and sleep disturbance in a patient with dementia with Lewy bodies. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(7):1543–5.

    Article  PubMed  Google Scholar 

  21. Shinno H, Yamanaka M, Ishikawa I, Danjo S, Nakamura Y, Inami Y, et al. Successful treatment of restless legs syndrome with the herbal prescription Yokukansan. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(1):252–3.

    Article  PubMed  Google Scholar 

  22. Miyaoka T, Furuya M, Yasuda H, Hayashia M, Inagaki T, Horiguchi J. Yi-gan san for the treatment of borderline personality disorder: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):150–4.

    Article  PubMed  Google Scholar 

  23. Miyaoka T, Furuya M, Yasuda H, Hayashida M, Nishida A, Inagaki T, et al. Yi-gan san as adjunctive therapy for treatment-resistant schizophrenia: an open-label study. Clin Neuropharmacol. 2009;32(1):6–9.

    Article  CAS  PubMed  Google Scholar 

  24. Miyaoka T, Furuya M, Yasuda H, Hayashida M, Nishida A, Inagaki T, et al. Yi-gan san for the treatment of neuroleptic-induced tardive dyskinesia: an open-label study. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(3):761–4.

    Article  CAS  PubMed  Google Scholar 

  25. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, et al. Yokukansan (TJ-54) for treatment of pervasive developmental disorder not otherwise specified and Asperger's disorder: a 12-week prospective, open-label study. BMC Psychiatry. 2012;12(1):215.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Egashira N, Iwasaki K, Ishibashi A, Hayakawa K, Okuno R, Abe M, et al. Repeated administration of Yokukansan inhibits DOI-induced head-twitch response and decreases expression of 5-hydroxytryptamine (5-HT)2A receptors in the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(6):1516–20.

    Article  CAS  PubMed  Google Scholar 

  27. Kanno H, Sekiguchi K, Yamaguchi T, Terawaki K, Yuzurihara M, Kase Y, et al. Effect of Yokukansan, a traditional Japanese medicine, on social and aggressive behaviour of para-chloroamphetamine-injected rats. J Pharm Pharmacol. 2009;61(9):1249–56.

    Article  CAS  PubMed  Google Scholar 

  28. Mizoguchi K, Tanaka Y, Tabira T. Anxiolytic effect of a herbal medicine, Yokukansan, in aged rats: involvement of serotonergic and dopaminergic transmissions in the prefrontal cortex. J Ethnopharmacol. 2010;127(1):70–6.

    Article  PubMed  Google Scholar 

  29. Nishi A, Yamaguchi T, Sekiguchi K, Imamura S, Tabuchi M, Kanno H, et al. Geissoschizine methyl ether, an alkaloid in Uncaria hook, is a potent serotonin(1)A receptor agonist and candidate for amelioration of aggressiveness and sociality by Yokukansan. Neuroscience. 2012;207:124–36.

    Article  CAS  PubMed  Google Scholar 

  30. Nogami A, Sakata Y, Uchida N, Yamaguchi K, Kawasaki C, Shindo T, et al. Effects of Yokukansan on anxiety-like behavior in a rat model of cerebrovascular dementia. J Nat Med. 2011;65(2):275–81.

    Article  PubMed  Google Scholar 

  31. Terawaki K, Ikarashi Y, Sekiguchi K, Nakai Y, Kase Y. Partial agonistic effect of Yokukansan on human recombinant serotonin 1A receptors expressed in the membranes of Chinese hamster ovary cells. J Ethnopharmacol. 2010;127(2):306–12.

    Article  PubMed  Google Scholar 

  32. Ueki T, Nishi A, Imamura S, Kanno H, Mizoguchi K, Sekiguchi K, et al. Effects of geissoschizine methyl ether, an indole alkaloid in Uncaria hook, a constituent of Yokukansan, on human recombinant serotonin(7) receptor. Cell Mol Neurobiol. 2012;33(1):129–35.

    Article  PubMed  Google Scholar 

  33. Doo AR, Kim SN, Park JY, Cho KH, Hong J, Eun-Kyung K, et al. Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cytotoxicity in vitro and in vivo. J Ethnopharmacol. 2010;131(2):433–42.

    Article  PubMed  Google Scholar 

  34. Kawakami Z, Ikarashi Y, Kase Y. Isoliquiritigenin is a novel NMDA receptor antagonist in kampo medicine Yokukansan. Cell Mol Neurobiol. 2011;31(8):1203–12.

    Article  CAS  PubMed  Google Scholar 

  35. Kawakami Z, Kanno H, Ueki T, Terawaki K, Tabuchi M, Ikarashi Y, et al. Neuroprotective effects of Yokukansan, a traditional Japanese medicine, on glutamate-mediated excitotoxicity in cultured cells. Neuroscience. 2009;159(4):1397–407.

    Article  CAS  PubMed  Google Scholar 

  36. Sekiguchi K, Kanno H, Yamaguchi T, Ikarashi Y, Kase Y. Ameliorative effect of Yokukansan on vacuous chewing movement in haloperidol-induced rat tardive dyskinesia model and involvement of glutamatergic system. Brain Res Bull. 2012;89(5–6):151–8.

    Article  CAS  PubMed  Google Scholar 

  37. Takeda A, Itoh H, Tamano H, Yuzurihara M, Oku N. Suppressive effect of Yokukansan on excessive release of glutamate and aspartate in the hippocampus of zinc-deficient rats. Nutr Neurosci. 2008;11(1):41–6.

    Article  CAS  PubMed  Google Scholar 

  38. Mizoguchi K, Shoji H, Tanaka Y, Tabira T. Ameliorative effect of traditional Japanese medicine Yokukansan on age-related impairments of working memory and reversal learning in rats. Neuroscience. 2011;177:127–37.

    Article  CAS  PubMed  Google Scholar 

  39. Uchida N, Egashira N, Iwasaki K, Ishibashi A, Tashiro R, Nogami A, et al. Yokukansan inhibits social isolation-induced aggression and methamphetamine-induced hyperlocomotion in rodents. Biol Pharm Bull. 2009;32(3):372–5.

    Article  CAS  PubMed  Google Scholar 

  40. Nakagawa T, Nagayasu K, Nishitani N, Shirakawa H, Sekiguchi K, Ikarashi Y, et al. Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of alpha(2)A-adrenoceptor. Neuroscience. 2012;227:336–49.

    Article  CAS  PubMed  Google Scholar 

  41. Yamada M, Hayashida M, Zhao Q, Shibahara N, Tanaka K, Miyata T, et al. Ameliorative effects of Yokukansan on learning and memory deficits in olfactory bulbectomized mice. J Ethnopharmacol. 2011;135(3):737–46.

    Article  PubMed  Google Scholar 

  42. Egashira N, Nogami A, Iwasaki K, Ishibashi A, Uchida N, Takasaki K, et al. Yokukansan enhances pentobarbital-induced sleep in socially isolated mice: possible involvement of GABA(A)-benzodiazepine receptor complex. J Pharmacol Sci. 2011;116(3):316–20.

    Article  CAS  Google Scholar 

  43. Kamei J, Miyata S, Ohsawa M. Involvement of the benzodiazepine system in the anxiolytic-like effect of Yokukansan (Yi-gan san). Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1431–7.

    Article  CAS  PubMed  Google Scholar 

  44. Kolb B, Pedersen B, Ballermann M, Gibb R, Whishaw IQ. Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities. J Neurosci. 1999;19(6):2337–46.

    CAS  PubMed  Google Scholar 

  45. Kuwagata M, Saito Y, Usumi K, Ono H, Nagao T. Disruption of brain development in male rats exposed prenatally to 5-bromo-2'-deoxyuridine. Congenit Anom (Kyoto). 2001;41(4):312–20.

    Article  CAS  Google Scholar 

  46. Ogawa T, Kuwagata M, Muneoka KT, Shioda S. Neuropathological examination of fetal rat brain in the 5-bromo-2'-deoxyuridine-induced neurodevelopmental disorder model. Congenit Anom (Kyoto). 2005;45(1):14–20.

    Article  Google Scholar 

  47. Kuwagata M, Muneoka KT, Ogawa T, Takigawa M, Nagao T. Locomotor hyperactivity following prenatal exposure to 5-bromo-2'-deoxyuridine: neurochemical and behavioral evidence of dopaminergic and serotonergic alterations. Toxicol Lett. 2004;152(1):63–71.

    Article  CAS  PubMed  Google Scholar 

  48. Muneoka K, Kuwagata M, Iwata M, Shirayama Y, Ogawa T, Takigawa M. Dopamine transporter density and behavioral response to methylphenidate in a hyperlocomotor rat model. Congenit Anom (Kyoto). 2006;46(3):155–9.

    Article  CAS  Google Scholar 

  49. Orito K, Morishima A, Ogawa T, Muneoka K, Kuwagata M, Takata J, et al. Characteristic behavioral anomalies in rats prenatally exposed to 5-bromo-2'-deoxyuridine. Int J Dev Neurosci. 2009;27(1):81–6.

    Article  CAS  PubMed  Google Scholar 

  50. Kuwagata M, Nagao T. Behavior and reproductive function of rat male offspring treated prenatally with 5-bromo-2'-deoxyuridine. Reprod Toxicol. 1998;12(5):541–9.

    Article  CAS  PubMed  Google Scholar 

  51. Kuwagata M, Muneoka K, Ogawa T, Shioda S. Effects of the genotoxic agent 5-bromo-2'-deoxyuridine with or without pre-pubertal gonadectomy on brain monoamines and their metabolites in female rats. Brain Res Bull. 2011;85(3–4):207–11.

    Article  CAS  PubMed  Google Scholar 

  52. Muneoka KT, Takigawa M. A neuroactive steroid, pregnenolone, alters the striatal dopaminergic tone before and after puberty. Neuroendocrinology. 2002;75(5):288–95.

    Article  CAS  PubMed  Google Scholar 

  53. Kuwagata M, Ogawa T, Muneoka K, Shioda S. Hyperactivity induced by prenatal BrdU exposure across several experimental conditions. Congenit Anom (Kyoto). 2011;51(4):177–82.

    Article  CAS  Google Scholar 

  54. Kuwagata M, Ogawa T, Nagata T, Shioda S. The evaluation of early embryonic neurogenesis after exposure to the genotoxic agent 5-bromo-2'-deoxyuridine in mice. Neurotoxicology. 2007;28(4):780–9.

    Article  CAS  PubMed  Google Scholar 

  55. Glick SD, Hinds PA, Baird JL. Two kinds of nigrostriatal asymmetry: relationship to dopaminergic drug sensitivity and 6-hydroxydopamine lesion effects in Long-Evans rats. Brain Res. 1988;450(1–2):334–41.

    Article  CAS  PubMed  Google Scholar 

  56. Glick SD, Carlson JN. Regional changes in brain dopamine and serotonin metabolism induced by conditioned circling in rats: effects of water deprivation, learning and individual differences in asymmetry. Brain Res. 1989;504(2):231–7.

    Article  CAS  PubMed  Google Scholar 

  57. Kyzar EJ, Pham M, Roth A, Cachat J, Green J, Gaikwad S, et al. Alterations in grooming activity and syntax in heterozygous SERT and BDNF knockout mice: the utility of behavior-recognition tools to characterize mutant mouse phenotypes. Brain Res Bull. 2012;89(5–6):168–76.

    Article  CAS  PubMed  Google Scholar 

  58. Roth A, Kyzar EJ, Cachat J, Stewart AM, Green J, Gaikwad S, et al. Potential translational targets revealed by linking mouse grooming behavioral phenotypes to gene expression using public databases. Prog Neuropsychopharmacol Biol Psychiatry. 2013;40:312–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Berridge KC, Whishaw IQ. Cortex, striatum and cerebellum: control of serial order in a grooming sequence. Exp Brain Res. 1992;90(2):275–90.

    Article  CAS  PubMed  Google Scholar 

  60. D'Agata V, Drago F, Serapide F, Cicirata F. Effects of cerebellectomy on motivation-related behavior: a time-course study. Physiol Behav. 1993;53(1):173–6.

    Article  PubMed  Google Scholar 

  61. Hartgraves SL, Randall PK. Dopamine agonist-induced stereotypic grooming and self-mutilation following striatal dopamine depletion. Psychopharmacology (Berl). 1986;90(3):358–63.

    Article  CAS  Google Scholar 

  62. Dunn AJ, Berridge CW, Lai YI, Yachabach TL. CRF-induced excessive grooming behavior in rats and mice. Peptides. 1987;8(5):841–4.

    Article  CAS  PubMed  Google Scholar 

  63. Van Erp AM, Kruk MR, Van Oers HJ, Hemmers NM. Differential effect of ACTH1-24 and alpha-MSH induced grooming in the paraventricular nucleus of the hypothalamus. Brain Res. 1993;603(2):296–301.

    Article  PubMed  Google Scholar 

  64. Van Erp AM, Kruk MR, De Kloet ER. Induction of grooming in resting rats by intracerebroventricular oxytocin but not by adrenocorticotropic hormone-(1–24) and alpha-melanocyte-stimulating hormone. Eur J Pharmacol. 1993;232(2–3):217–21.

    Article  PubMed  Google Scholar 

  65. Duxon MS, Stretton J, Starr K, Jones DN, Holland V, Riley G, et al. Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement. Psychopharmacology (Berl). 2001;153(2):203–9.

    Article  CAS  Google Scholar 

  66. Kennett GA, Ainsworth K, Trail B, Blackburn TP. BW 723C86, a 5-HT2B receptor agonist, causes hyperphagia and reduced grooming in rats. Neuropharmacology. 1997;36(2):233–9.

    Article  CAS  PubMed  Google Scholar 

  67. Dunn AJ, Guild AL, Kramarcy NR, Ware MD. Benzodiazepines decrease grooming in response to novelty but not ACTH or beta-endorphin. Pharmacol Biochem Behav. 1981;15(4):605–8.

    Article  CAS  PubMed  Google Scholar 

  68. Nin MS, Ferri MK, Couto-Pereira NS, Souza MF, Azeredo LA, Agnes G, et al. The effect of intra-nucleus accumbens administration of allopregnanolone on delta and gamma2 GABA(A) receptor subunit mRNA expression in the hippocampus and on depressive-like and grooming behaviors in rats. Pharmacol Biochem Behav. 2012;103(2):359–66.

    Article  CAS  PubMed  Google Scholar 

  69. Bolivar VJ, Danilchuk W, Fentress JC. Separation of activation and pattern in grooming development of weaver mice. Behav Brain Res. 1996;75(1–2):49–58.

    Article  CAS  PubMed  Google Scholar 

  70. Strazielle C, Lalonde R. Grooming in Lurcher mutant mice. Physiol Behav. 1998;64(1):57–61.

    Article  CAS  PubMed  Google Scholar 

  71. Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature. 2012;488(7413):647–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Matthiessen L, Kia HK, Daval G, Riad M, Hamon M, Verge D. Immunocytochemical localization of 5-HT1A receptors in the rat immature cerebellum. Neuroreport. 1993;4(6):763–6.

    Article  CAS  PubMed  Google Scholar 

  73. Miquel MC, Kia HK, Boni C, Doucet E, Daval G, Matthiessen L, et al. Postnatal development and localization of 5-HT1A receptor mRNA in rat forebrain and cerebellum. Brain Res Dev Brain Res. 1994;80(1–2):149–57.

    Article  CAS  PubMed  Google Scholar 

  74. Oostland M, van Hooft JA. The role of serotonin in cerebellar development. Neuroscience. 2013;248C:201–12.

    Article  Google Scholar 

  75. Sekerkova G, Ilijic E, Mugnaini E. Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat. J Comp Neurol. 2004;470(3):221–39.

    Article  PubMed  Google Scholar 

  76. del Olmo E, Lopez-Gimenez JF, Vilaro MT, Mengod G, Palacios JM, Pazos A. Early localization of mRNA coding for 5-HT1A receptors in human brain during development. Brain Res Mol Brain Res. 1998;60(1):123–6.

    Article  PubMed  Google Scholar 

  77. Chugani DC. Role of altered brain serotonin mechanisms in autism. Mol Psychiatry. 2002;7 Suppl 2:S16–7.

    Article  PubMed  Google Scholar 

  78. Chugani DC, Sundram BS, Behen M, Lee ML, Moore GJ. Evidence of altered energy metabolism in autistic children. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23(4):635–41.

    Article  CAS  PubMed  Google Scholar 

  79. Sokol DK, Edwards-Brown M. Neuroimaging in autistic spectrum disorder (ASD). J Neuroimaging. 2004;14(1):8–15.

    Article  PubMed  Google Scholar 

  80. Pierce K, Courchesne E. Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism. Biol Psychiatry. 2001;49(8):655–64.

    Article  CAS  PubMed  Google Scholar 

  81. Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci. 2005;23(2–3):183–7.

    Article  PubMed  Google Scholar 

  82. Kawakami Z, Ikarashi Y, Kase Y. Glycyrrhizin and its metabolite 18 beta-glycyrrhetinic acid in glycyrrhiza, a constituent herb of Yokukansan, ameliorate thiamine deficiency-induced dysfunction of glutamate transport in cultured rat cortical astrocytes. Eur J Pharmacol. 2010;626(2–3):154–8.

    Article  CAS  PubMed  Google Scholar 

  83. Pawlak CR, Ho YJ, Schwarting RK. Animal models of human psychopathology based on individual differences in novelty-seeking and anxiety. Neurosci Biobehav Rev. 2008;32(8):1544–68.

    Article  PubMed  Google Scholar 

  84. Thiel CM, Muller CP, Huston JP, Schwarting RK. High versus low reactivity to a novel environment: behavioural, pharmacological and neurochemical assessments. Neuroscience. 1999;93(1):243–51.

    Article  CAS  PubMed  Google Scholar 

  85. Kondoh M, Shiga T, Okado N. Regulation of dendrite formation of Purkinje cells by serotonin through serotonin1A and serotonin2A receptors in culture. Neurosci Res. 2004;48(1):101–9.

    Article  CAS  PubMed  Google Scholar 

  86. Whitaker-Azmitia PM, Murphy R, Azmitia EC. Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology. Brain Res. 1990;528(1):155–8.

    Article  CAS  PubMed  Google Scholar 

  87. Miczek KA, Weerts EM, Vivian JA, Barros HM. Aggression, anxiety and vocalizations in animals: GABAA and 5-HT anxiolytics. Psychopharmacology (Berl). 1995;121(1):38–56.

    Article  CAS  Google Scholar 

  88. Lucki I. Serotonin receptor specificity in anxiety disorders. J Clin Psychiatry. 1996;57 Suppl 6:5–10.

    PubMed  Google Scholar 

Download references

Acknowledgments

We appreciate Prof. Katsutoshi Terasawa, Chiba Central Medical Center, for his helpful comments and excellent suggestions.

Conflict of Interest

The authors declare no conflict of interests.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katsumasa Muneoka.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Muneoka, K., Kuwagata, M., Ogawa, T. et al. Mother/Offspring Co-administration of the Traditional Herbal Remedy Yokukansan During the Nursing Period Influences Grooming and Cerebellar Serotonin Levels in a Rat Model of Neurodevelopmental Disorders. Cerebellum 14, 86–96 (2015). https://doi.org/10.1007/s12311-014-0611-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-014-0611-2

Keywords

Navigation