| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1992: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Research Abstract |
We have proposed that DOPA itself is a neuroactive substance. Using striatal microdialysis, characteristics of DOPA release and relevance of endogenous or exogenous DOPA to locomotor activities (1.a.) of rats were studied. 1. Release ratio of DOPA:dopamine (DA) was 1:2. The basal DOPA release was Ca^<2+>-dependent and tetrodotoxin (TTX, 1 muM)-sensitive similary as DA. 2. Infusion of nicotine (10-300 mum) through dialysis membrane concentration-dependently released endogenous DOPA. This evoked release at 200 muM was Ca^<2+>-dependent, stereoselective, TTX (100 nM)- and mecamylamine (500 muM)-sensitive. The basal release of DOPA, but not of DA, was mecamylamine-sensitive. 3. Nicotine (0.1-1.0 mg/kg,s.c.) dose-dependently increased 1.a. This effect at 0.4 mg/kg was stereoselective and mecamylamine (1.0 mg/kg, s.c.)-sensitive. A very low i.p. dose of alpha-methyl-p-tyrosine, 3 mg/kg, inhibited the basal release of DOPA without decreasing that of DA. Pretreatment with this dose inhibited t
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he nicotine (0.4 mg/kg)-induced increases in 1.a. Endogenously released DOPA is probably relevant to the nicotine-induced increases in 1.a. 4. Exogenous L-DOPA (100 mg/kg, i.p.) markedly increased the DOPA release and 1.a. under inhibition of central DOPA decarboxylase. The DOPA release reached a peak 1 h after injection, then gradually declined. Increase in 1.a. began to start at the peak of DOPA release, reached a peak 3 h after injection, then gradually declined. DA release began to increase 100 min after injection and remained increased, even after 1.a. restored. L-DOPA 30 mg/kg alone produced no effect on 1.a. Quinpirole 1.0 mg/kg (s.c.), a selective D_2-agonist, increased 1.a. Simultaneous application of noneffective 30 mg/ka L-DOPA potentiated quinpirole (0.1 and 1 mg/kg)-induced increases in 1.a., before the elevation of DA release was seen. D-DOPA produced no potentiation. L-DOPA is a potentiator for probably postsynaptic D_2-receptors. This explains some of mechanisms for clinical experience that L-DOPA and D_2-agonist are synergistic for Parkinson's disease. Less
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