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

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. 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. 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. These findings suggest that 5-HT1B receptor-AC-PKA signal pathway in the BLA is involved in the regulation of PD-related anxiety.