Effect of diazepam and yohimbine on neuronal activity in sham and hemiparkinsonian rats

- Diazepam affects anterior cingulate activity in sham, but not in parkinsonian rats.
- Yohimbine affects amygdala activity in sham, but not in parkinsonian rats.
- Diazepam or yohimbine has no effect on cortical oscillations in either animal group.

The prefrontal cortex and the amygdala are critical for the emotional guidance of behavior and are believed to be a site of action for many anxiolytics and anxiogenics. Despite extensive studies examining how these drugs affect behavior, there is little information regarding their effects on neuronal activity. Additionally, with recent recognition of anxiety as a non-motor symptom of Parkinson's disease, it is unknown if activity in the cortex and the amygdala is altered. Previously, we reported that hemiparkinsonian rats had higher baseline anxiety-like behavior and diminished responsiveness to the acute anxiolytic, diazepam. In contrast, sham-lesioned rats exhibited anxiolytic behavior to diazepam. In this study, we monitored in vivo single-unit spiking activity simultaneously from the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA) in anesthetized sham-lesioned and hemiparkinsonian rats to unmask neuro-circuits underpinning the difference in diazepam responsiveness. We found that baseline spiking activity in the ACC was the same in both sham and hemiparkinsonian rats. We also noted a similar phenomenon for baseline activity in the BLA between sham and hemiparkinsonian rats. However, neuronal spiking activity after diazepam administration (1.5 mg/kg, SubQ) was lower than in controls in the ACC of sham-lesioned rats whereas no difference was noted after diazepam treatment in hemiparkinsonian rats. BLA neuronal spiking activity was unaffected by diazepam administration in either animal group. On the other hand, yohimbine treatment (5 mg/kg, SubQ) coincided with lower neuronal spiking activity compared to controls in the BLA of sham-lesioned rats, but was unchanged from controls in hemiparkinsonian rats. Yohimbine did not affect ACC neuronal spiking activity in either group. Overall, the lack of ACC responsiveness to diazepam in hemiparkinsonian, but not sham-lesioned rats underscores a plausible fundamental difference in anxiety-related neural signaling between animal groups.