RT Journal Article
SR Electronic
T1 Self-Injurious Behavior and Dopaminergic Neuron System in Neonatal 6-Hydroxydopamine-Lesioned Rat: 2. Intracerebral Microinjection of Dopamine Agonists and Antagonists
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1031
OP 1037
VO 280
IS 2
A1 Hitoshi Okamura
A1 Tsuyoshi Murakami
A1 Chihiro Yokoyama
A1 Toru Nakamura
A1 Yasuhiko Ibata
YR 1997
UL http://jpet.aspetjournals.org/content/280/2/1031.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics