Properties of rotational behaviour produced by methylxanthine derivatives in mice with unilateral striatal 6-hydroxydopamine-induced lesions.

Abstract

The present investigation was undertaken to study effects of methylxanthine derivatives on rotational behavior 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 .apprx. 40 min. When L-dopa 10 mg/kg was given to mice in combination with theophylline 25 mg/kg, total turns for 2 h were significantly higher than those of L-dopa and theophylline dose. 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 < 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 suppressed by spiroperiodol, at a dose higher than that to apomorphine or methamphetamine. Methylxanthine derivatives produce contralateral rotational behavior due to not only phosphodiesterase inhibition but dopamine receptor stimulation.