Conditioning of the early behavioral response to apomorphine in the rotational model of Parkinson's disease

Abstract

The rotational model of Parkinson's disease has been widely used to investigate the action of dopamine agonists. This animal model involves the production of a unilateral nigrostriatal lesion in rats. The lesion is produced with 6-hydroxydopamine which causes dopamine depletion and subsequent supersensitivity of striatal receptors. Thus, administration of drugs which are therapeutically effective in Parkinson's disease, elicits circling behavior contralateral to the lesioned side. The origin of the paradoxical response and the undrugged rotations observed after saline injections in apomorphine pretreated rats has not been explained. We report here that the undrugged response can be associated with the early rotational response elicited by the drug. Furthermore, we show the effect of inhibitory conditioning on this early response. Our results suggest that pharmacological conditioning plays a significant role in the modification of the therapeutic effectiveness of CNS-active drugs after extended treatments.