A comparison of circling models for the detection of antiparkinson activity

Apomorphine, d-amphetamine, methylphenidate, nomifensine, ET495 and amantadine each induced a dose-dependent stereotyped behaviour in the rat. L-Dopa was inactive in the absence of any pretreatment. The behaviour induced by apomorphine, methylphenidate, nomifensine and amantadine persisted following pretreatment with a-methylparatyrosine. However, only the effect of apomorphine developed following combined pretreatment with reserpine/a-methylparatyrosine. The effects of all stereotypic agents were inhibited by haloperidol, apomorphine, methylphenidate and nomifensine being most resistant. All agents, including L-Dopa, induced a dose-dependent contralateral circling behaviour in animals with asymmetric lesion of the medial raphé nucleus and a dose-dependent ipsilateral circling after unilateral lesion of the substantia nigra. Following unilateral lesions in the ventromedial area of the medial forebrain bundle (medial to the substantia nigra and carrying 5-hydroxytryptamine neurones) amphetamine caused an ipsilateral circling behaviour, amantadine a behaviour which was characterised by definite bursts in either direction, and all other agents caused contralateral circling.