Place conditioning to apomorphine in rat models of Parkinson's disease: Differences by dose and side-effect expression

Abstract

One potential complication of treating Parkinson's Disease (PD) with dopaminergic drugs is dopamine dysregulation syndrome, an addiction-like response to the drug therapy. Here, we assessed whether rats given parkinsonian-like symptoms with a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle (6-OHDA-MFB), exhibit similar behavior. To examine this, we injected these rats or sham-lesioned rats subcutaneously (sc) with apomorphine (APO) at low (0.05mg/kg) and high (1mg/kg) dosage and monitored their conditioned place preference Saline was administered on alternating days. After 4 and 8 conditioned pairings, both rat groups underwent post-conditioning tests in a drug-free state 6-OHDA rats exhibited positive place conditioning to the low dose of APO after 4 and 8 pairings whereas sham-lesioned rats did not (p<0.01). At the high APO dose, sham-lesioned rats showed consistent positive place conditioning, but preferences in 6-OHDA rats were more variable although they all exhibited rotation behavior. Upon further inspection, we noted that contraversive rotation increased over time and this negatively correlated with place conditioning scores. While the absolute number of rotations did not negatively affect preference for the APO-paired chamber, an increase in rotation numbers between pairings did (r=−0.634, p=0.027). Taken together, 6-OHDA rats were more sensitive to the rewarding aspects of APO, but the adverse consequence of rotation diminished this response This model may be ideal to study addiction-like responses in PD.