Self-Injurious Behavior and Dopaminergic Neuron System in Neonatal 6-Hydroxydopamine-Lesioned Rat: 1. Dopaminergic Neurons and Receptors1

  1. Chihiro Yokoyama2,1 and
  2. Hitoshi Okamura2
  1. 1Department of Anatomy, Kyoto Prefectural University of Medicine (C.Y.), Kyoto 602, Japan, and 2Department of Anatomy and Brain Science, Kobe University School of Medicine (H.O.), Kobe 650, Japan

    Abstract

    Dopaminergic neuronal circuits underlying self-injurious behavior (SIB) were investigated in neonatal 6-hydroxydopamine (6-OHDA)-induced dopamine-depleted rats. The extent of damaged dopamine neuronal areas was investigated by quantitative analysis of tyrosine hydroxylase (TH) immunocytochemistry and the biochemical quantification of dopamine levels in three groups; neonatal 6-OHDA-treated rats showing SIB (the SIB(+) group), neonatal 6-OHDA-treated rats not showing SIB (SIB(-) group) and neonatal saline-treated controls (control group). In the SIB(+) group, both dorsal and ventral mesostriatal dopaminergic neuron systems were severely destroyed, but the mesocortical dopaminergic neuron system and intrahypothalamic dopaminergic neuron system remained intact. In SIB(-) group, the dorsal mesostriatal dopaminergic neuron system was severely destroyed, but the ventral mesostriatal dopaminergic neuron system was only partially impaired. The effect of neonatal 6-OHDA treatment on dopaminergic receptors was analyzed by quantitative in vitro receptor autoradiography using [3H]SCH-23390 for the D1 site and [3H]YM-09151–2 for the D2 site. Although D1 and D2 binding was not altered in the dorsal and ventral striatum, cerebral cortex and hypothalamus, the D1 binding in the substantia nigra pars reticulata was increased in the SIB(+) group compared with the SIB(-) or control groups. The D1 binding assay using the membrane preparation of the nigral homogenates, revealed that theK D did not change, but the Bmaxin the SIB(+) group was higher than that in the SIB(-) or control groups (P < .05). These results suggest that the region-specific change of dopaminergic neurons and receptors underlies the manifestation of SIB.

    Footnotes

    • Send reprint requests to: Dr. H. Okamura, Department of Anatomy and Brain Science, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.

    • ↵1 This work was supported in parts by grants to H.O. from Uehara Memorial Foundation, Ciba-Geigy Foundation, and Ministry of Education, Science and Culture, Japan.

    • ↵2 Current address: Department of Anatomy, Kawasaki Medical School, Kurashiki 701–01, Japan.

    • Abbreviations:
      CPDL
      the dorsolateral part of the caudate-putamen
      CPM
      the medial part of the caudate-putamen
      CPPV
      the periventricular part of the caudate-putamen
      CPVL
      the ventrolateral part of the caudate-putamen
      DAB
      diaminobenzidine
      HPRT
      hypoxanthine-guanine phosphoribosyl transferase
      L-DOPA
      dihydroxyphenylalanine
      6-OHDA
      6-hydroxydopamine
      PBS
      phosphate-buffered saline
      SIB
      self-injurious behavior
      SNR
      substantia nigra pars reticulata
      TH
      tyrosine hydroxylase
      TH-IR
      tyrosine hydroxylase-immunoreactive
      VTA
      ventral tegmental area
      ANOVA
      analysis of variance
      HPLC
      high-performance liquid chromatography
      • Received October 3, 1995.
      • Accepted October 11, 1996.
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    1. JPET February 1, 1997 vol. 280 no. 2 1016-1030
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