EFFECTS OF A SINGLE AND REPEATED ADMINISTRATION OF MORPHINE ON ROTATIONAL BEHAVIOR MODEL OF MICE AND RATS WITH UNILATERAL LESIONS OF NIGROSTRIATAL DOPAMINERGIC SYSTEM

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 α-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 α-methyl p-tyrosine or spiroperiodol did not suppress significantly morphine-induced contralateral rotation. Development of tolerance to contralateral rotation was not observed after repeated administrations. It is concluded that 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-OHDA lesions, morphine produced ipsilateral rotation in parallel with a decrease of catalepsy and an increase of behavioural excitation. Tolerance to ipsilateral rotation developed following repeated administrations of morphine. Contralateral rotation produced by levallorphan in tolerant rats was suggested to be an abstinence sign. © 1979, The Pharmaceutical Society of Japan. All rights reserved.