Context-driven changes in L-DOPA-induced behaviours in the 6-OHDA lesioned rat.

ABSTRACT

Both contralateral rotational behaviour and dyskinetic abnormal involuntary movements (AIMs) are induced by the administration of l-DOPA in the unilateral 6-OHDA lesioned rat model of Parkinson's disease. Since rotational responses can be conditioned to environmental cues we have investigated the extent to which drug-induced AIMS may also be conditioned by exteroceptive cues and experience. In Experiment I, 6-OHDA lesioned rats received repeated daily injections of l-DOPA either in their home cage (control) or in association with a brief (20 mins) exposure to the rotometers (paired). To assess conditioning, all animals then received two tests in the rotometer bowls. Following injection of saline the paired group both rotated more contralaterally and displayed manifest AIMs, neither of which were exhibited by the control rats. Moreover, following injection of l-DOPA, the paired group showed a trend for increased AIMs compared to controls. Two further studies provided longer exposure to the conditioning environments in counterbalanced designs. Although, using these parameters, re-exposure in the presence of saline did not induce context-dependent AIMs, a strong context-specific component of the sensitised response to l-DOPA was seen; chronic administration of drug produced a significantly stronger behavioural response in animals paired with a particular environment for drug administration than controls. This data suggests that part of the sensitisation of behavioural responding to l-DOPA administration is not solely a pharmacological phenomenon, but is also conditioned to the environmental context in which the drug is administered. This has clear implications for the clinical observation and experimental measurement of drug-induced dyskinesia in Parkinson's disease patients and animal models.