Abstract
Intracisternal 6-hydroxydopamine treatment to newborn rats caused massive and permanent damage of brain dopaminergic neurons, and many of these animals show self-injurious behavior (SIB) when loaded by systemic injection of L-dihydroxyphenuylalanine (L-DOPA) or D1 agonist, SKF-38393. SIB occurred at life-long time in neonatal 6-hydroxydopamine-lesioned rats, because SIB confirmed rats at 4 to 6 wk all showed SIB at 3 to 5 mo and at 12 to 13 mo after L-DOPA loading. To elucidate the brain locus important for the induction and cessation of SIB, in our study, we microinjected dopamine agonists and antagonists into various dopamine neuron innervating areas. L-DOPA-induced SIB was inhibited by the injection of a D1antagonist, SCH-23390 (5 μg), into the bilateral substantia nigra, but not into the bilateral caudate-putamen or nucleus accumbens. The microinjection of YM-09151–2 (10 μg), a D2 antagonist, into these regions could not stop SIB. For examining the important area for the induction of SIB, we microinjected SKF-38393, D1agonist, and/or LY-141865, D2 agonist (each 1 μg) into bilateral (or ipsilateral) caudate-putamen and substantia nigra. SIB was induced only in the case of D1 and D2receptors in both the bilateral caudate putamen and bilateral substantia nigra being stimulated simultaneously by the mixed application of SKF-38393 and LY-141865. SIB was not induced by the sole injection of SKF-38393 into bilateral caudate-putamen or bilateral substantia nigra. These observations suggest that both caudate-putamen and nigral D1- and D2-like receptors are important for the induction of SIB, but, for cessation of SIB, up-regulated nigral D1 receptor is crucial.
Footnotes
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Send reprint requests to: Dr. Hitoshi Okamura, Department of Anatomy and Brain Science, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
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↵1 This work was supported in parts by grants to H. O. from Uehara Memorial Foundation, Ciba-Geigy Foundation, Smoking Research Foundation, and Ministry of Education, Science and Culture, Japan.
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↵2 Current address: Department of Anatomy, Kawasaki Medical School, Kurashiki 701–01, Japan.
- Abbreviations:
- Acb
- nucleus accumbens
- 6-OHDA
- 6-hydroxydopamine
- SIB
- self-injurious behavior
- SNR
- substantia nigra pars reticulata
- L-DOPA
- L-dihydroxyphenylalanine
- Received October 3, 1995.
- Accepted October 11, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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