Exploring aversion in an animal model of pre-motor stage Parkinson's disease

Documentation of several non-motor deficits in Parkinson's disease (PD) years prior to the onset of clinical motor symptoms has facilitated the exploration of several models to better understand the pre-motor features of the disease. Reports of aversion deficits in early stages of PD have led to the current study focused on neural and behavioral responses to aversion in a rat model of pre-motor PD. To gain insight into the pre-motor stage of PD, rats were administered low dosages of 6-hydroxydopamine in a step-wise manner and assessed at three weeks post the final treatment with behavioral and imaging measures. The pre-motor PD rats exhibited lower arousal and less avoidance behavior in the presence of an aversive odor. These results could not be attributed to selective hyposmia since the PD rats did not exhibit any deficit in the exploration of the odor. The imaging studies showed that the PD group had similar blood oxygenation level dependent (BOLD) activation in the olfactory regions, insular cortex and medial nucleus of amygdala as compared to the control and the sham lesioned groups, and significantly higher BOLD activation in the nucleus accumbens (NAcc). However significantly lower BOLD activation was observed in the basal, lateral and central nucleus of the amygdala in the PD group compared to sham and control animals. Taken together, our results suggest that aversion deficits in the pre-motor stages of the disease maybe a result of inappropriate response generation due to cortico-amygdalar dysfunction.