Effects of a single and repeated administration of morphine on rotational behaviour model of mice and rats with unilateral lesions of nigrostriatal dopaminergic system.

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Abstract
In mice with unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesions, morphine produced marked ipsilateral and slight contralateral rotations. Apomorphine and methamphetamine induced contralateral and ipsilateral rotations, respectively. Ipsilateral rotation produced by morphine increased in a dose-dependent manner. Pretreatment with .alpha.-methyl-p-tyrosine suppressed ipsilateral rotations induced by morphine or methamphetamine but not contralateral rotation by apomorphine. Spiroperidol inhibited rotations induced by morphine, methamphetamine or apomorphine. Repeated administrations of morphine caused a development of tolerance to ipsilateral rotation. Contralateral rotation induced by morphine did not increase dose-dependently. Pretreatment with .alpha.-methyl-p-tyrosine or spiroperidol did not suppress significantly morphine-induced contralateral rotation. Develpment of tolerance to contralateral rotation was not seen after repeated administrations. Apparently morphine induces ipsilateral rotation by mechanisms similar to those of methamphetamine while mechanisms of contralateral rotation induced by morphine appears to be different from those of ipsilateral rotation. In rats with unilateral intranigral 6-OHD lesions morphine produced ipsilateral rotation in parallel with a decrease of catalepsy and an increase of behavioral excitation. Tolerance to ipsilateral rotation developed after repeated administrations of morphine. Contralateral rotation produced by levallorphan in tolerant rats was apparently an abstinence sign.