Persistent behavioural effect of apomorphine in 6-hydroxydopamine-lesioned rats

Abstract

The rotational (circling) behaviour of rodents with unilateral nigrostriatal damage has been used extensively to investigate nigrostriatal function and the action of dopaminergic compounds¹. Rats lesioned by unilateral microinjection of the catecholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA), spontaneously exhibit slight ipsilateral (towards the lesioned side) rotation. Systemic challenge with the dopamine receptor agonist apomorphine induces active contralateral rotation, apparently as a result of supersensitivity in the lesioned hemisphere^2,3. We report here that apomorphine treatment also results in an extraordinarily persistent change in spontaneous (undrugged) rotation. After one treatment with 50 µg per kg apomorphine, exposure to the rotation environment resulted in a brief, intense burst of contralateral rotation. This behaviour, apparent for months after drug treatment, did not fully develop until 2 weeks after treatment and was never observed in lesioned, but otherwise drug-naive rats. The latent apomorphine effect, unlike the acute effect, was inversely related to dose over the range tested. The behaviour was relatively specific for the environment in which drug treatment had occurred, suggesting a role for learning, but it is difficult to reconcile the inverse dose–response function, lack of recency effect and inability to induce an analogous phenomenon using (+)amphetamine with this explanation.