Rotational behaviour in rats with unilateral striatal kainic acid lesions: a behavioural model for studies on intact dopamine receptors

Abstract

Rotational behaviour can be induced in rats with unilateral kainic acid induced degeneration of the neostriatum and adjacent regions by means of dopaminergic drugs. Kainic acid lesioned rats, when challenged with apomorphine or the ergot compounds elymoclavine, lergotrile and bromocriptine, perform dose-related turning towards the lesioned side. Blockade of the rotations by a number of dopamine receptor antagonists indicates dopaminergic involvement. Since kainic acid treatment had previously been shown to reduce the number of dopamine receptors in the injected brain regions, ipsilateral turning behaviour elicited by dopaminergic drugs after these lesions seems to be due to intact receptors on the contralateral hemisphere. Comparison of rotation data from experiments at intact dopamine receptors with those from experiments at supersensitive dopamine receptors revealed: (1) A marked decrease of the threshold dose for induction of rotational behaviour in the 6-OHDA lesioned rats. This decrease is particularly pronounced for lergotrile and bromocriptine. (2) A higher peak activity of rotations in rats with supersensitive dopamine receptors. (3) A considerable increase in the slope values of logits plots following denervation of dopamine receptors. Thus, the present report suggests: (a) that a behavioural model for studies of drugs acting at intact dopamine receptors can be obtained by unilateral neostriatal kainate injections and (b) that development of dopaminergic supersensitivity involves increased affinity of the receptors for dopamine receptor agonists and an increase in the coupling to its biological effector mechanism.