5-HT1B receptors in the basolateral amygdaloid nucleus regulate anxiety-like behaviors through AC-PKA signal pathway in a rat model of Parkinson's disease

Background: Parkinson's disease (PD) is commonly accompanied with anxiety, multiple studies indicate that the basolateral amygdaloid nucleus (BLA) is closely related to modulation of anxiety and expresses serotonin1B (5-HT1B) receptors, however, effects of BLA 5-HT1B receptors on anxiety-like behaviors are unclear, particularly in PD-related anxiety. Methods: The open-field and elevated plus maze tests were used to examine anxiety-like behaviors. In vivo electrophysiology and microdialysis were performed to observe the firing activity of BLA neurons and GABA, glutamate, dopamine (DA) and 5-HT release in the BLA, respectively. Western blotting was used to analyze protein expression of 5-HT1B receptors, adenylate cyclase (AC) and phosphorylated protein kinase A at threonine 197 site (p-PKA-Thr197) in the BLA. Results: Intra-BLA injection of 5-HT1B receptor agonist CP93129 produced anxiety-like effects and antagonist SB216641 induced anxiolytic-like responses in sham-operated and 6-hydroxydopamine-lesioned rats. Further, pretreatment with AC inhibitor SQ22536 and PKA inhibitor KT5720 blocked the behavioral effects of CP93129, respectively. Intra-BLA injection of CP93129 increased the firing rate of BLA glutamate neurons and decreased GABA/glutamate ratio and DA and 5-HT levels in the BLA of sham-operated and the lesioned rats, while SB216641 induced the opposite effects. Compared with sham-operated rats, effects of CP93129 and SB216641 on behaviors, electrophysiology and microdialysis were decreased in the lesioned rats, which were associated with decreased expression of 5-HT1B receptors, AC and p-PKA-Thr197 in the BLA. Conclusion: These findings suggest that 5-HT1B receptor-AC-PKA signal pathway in the BLA is involved in the regulation of PD-related anxiety.

Automated summary

This study found that the BLA's 5-HT1B receptors regulate anxiety-like behavior, but the effects on PD-related anxiety are unclear. The results showed that the 5-HT1B receptor agonist induced anxiety-like effects, while the antagonist produced anxiolytic-like responses. Further investigation revealed the involvement of the AC-PKA signaling pathway in this process.