Vol. 280, Issue 2, 1031-1037, 1997

Self-Injurious Behavior and Dopaminergic Neuron System in Neonatal 6-Hydroxydopamine-Lesioned Rat: 2. Intracerebral Microinjection of Dopamine Agonists and Antagonists¹

Hitoshi Okamura, Tsuyoshi Murakami, Chihiro Yokoyama² , Toru Nakamura and Yasuhiko Ibata

Department of Anatomy and Brain Science, Kobe University School of Medicine (H.O.), Kobe 650, Japan, and Departments of Anesthesiology (T.M.), Anatomy (C.Y.) and Dental Science (T.N.), Kyoto Prefectural University of Medicine, Kyoto 602, Japan

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 D₁ antagonist, 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, D₁ agonist, 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 D₂ receptors 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.