Objective: To (1) examine whether anxiety-like behavior is more prevalent in Parkinsonian compared to non-Parkinsonian rats, (2) evaluate the efficacy of diazepam in Parkinsonian and non-Parkinsonian rats, and (3) evaluate the effect of diazepam on neuronal spiking activity of the anterior cingulate cortex or basolateral amygdala.

Background: There is growing recognition that anxiety has a greater impact on the quality of life in Parkinson’s disease (PD) than motor symptoms. Yet, little is known about the pathophysiology underlying anxiety present in 25-51% of PD patients, posing a considerable barrier in developing effective treatment strategies.

Methods: We used the unilateral, medial forebrain bundle 6-hydroxydopamine (6-OHDA) late-stage rat model of PD (‘PD rat’) to assess baseline anxiety-like behavior based on their performance in the elevated plus maze (EPM). Next, we administered diazepam prior to EPM, open field test (OFT), and marble burying testing to unmask differences in efficacy between sham and PD rats. Lastly, we employed in vivo electrophysiology to monitor neuronal spiking activity in the anterior cingulate cortex (ACC), and the basolateral amygdala (BLA), key regions in the limbic circuit, during administration of diazepam in sham and PD animals.

Results: There is a greater prevalence of high anxiety rats in the Parkinsonian group and Parkinsonian rats have higher baseline anxiety-like behavior than sham and naïve rats. We also found that diazepam (1.5 mg/kg) was less effective in high anxiety PD rats in the EPM and OFT than high anxiety sham rats, suggesting differences in neurocircuits involved in anxiety. Diazepam decreased ACC neuronal spiking activity in sham rats, but not in PD rats or in the BLA of either animal group.

Conclusions: Our findings posit that anxiety in PD and non-PD may differ due to differences in neurocircuits in limbic brain areas and understanding these differences can lead to improved treatment of PD non-motor symptoms.

Presented in part at the Society for Neuroscience on 10/21/15.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/fundamental-differences-in-parkinsonian-rat-limbic-regions-contribute-to-anxious-behavior-and-diminished-responsiveness-to-diazepam/