PROPERTIES OF ROTATIONAL BEHAVIOUR PRODUCED BY METHYLXANTHINE DERIVATIVES IN MICE WITH UNILATERAL STRIATAL 6-HYDROXYDOPAMINE-INDUCED LESIONS

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The present investigation was undertaken to study effects of methylxanthine derivatives on rotational behaviour produced by dopamine receptor stimulating drugs and properties of methylxanthine-induced rotation in mice with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the striatum. L-Dopa 10 mg/kg, i.p., produced contralateral turning which lasted for about 40 min. When L-dopa 10 mg/kg was biven to mice in combination with theophylline 25 mg/kg, total turns for 2 hr were significantly higher than those of L-dopa and theophylline alone. Caffeine and theophylline in doses of 25 and 50 mg/kg, i.p., respectively, produced marked increase in contralateral rotation in a dose-dependent manner in mice with lesions. Theobromine 100 mg/kg, i.p., also produced a moderate contralateral rotation. Total turns of ipsilateral rotation produced by methylxanthine derivatives were less than 10% of those of contralateral circling. Theophylline-induced contralateral rotation was reduced to nearly 30% of the control by alpha-methyl-p-tyrosine (alpha-MPT). It was also suppressed by spiroperidol, at a dose higher than that to apomorphine or methamphetamine. These results suggest that methylxanthine derivatives produce contralateral rotational behaviour due to not only phosphodiesterase inhibition but also dopamine receptor stimulation.
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