Parkinson's disease (PD) is a neurodegenerative disease that causes a movement disorder. It is classically characterized by motor disabilities such as tremor, bradykinesia, rigidity and postural instability (Decourt et al., 2021). Moreover, a variety of non-motor symptoms including anxiety, depression and cognitive deficit are increasingly recognized in PD (Khatri et al., 2020; Marinus et al., 2018). Although anxiety is common in PD, the underlying mechanism has been clarified.

The bed nucleus of stria terminalis (BNST) is a limbic forebrain structure, which has a dense collection of subnuclei (Alheid and Heimer, 1988). The BNST is divided into anterior and posterior divisions and further subdivided into a dorsal-ventral portion by the anterior commissure in the rodents (Vranjkovic et al., 2017). Accumulating evidence from both rodents and human suggests that the BNST is involved in a broad range of affective states and behaviors, such as anxiety (Waddell et al., 2006; Adhikari, 2014; McMenamin et al., 2014). It is also known that the anteroventral BNST (avBNST) is closely related to anxiety disorders, because studies find the alteration of neuronal activity of the avBNST when exposed to different anxiogenic stressors (Butler et al., 2016; Sajdyk et al., 2008). Further, our recent study reveals the key role of the avBNST in the regulation of anxiety-like behaviors, because the GABAergic projections from the avBNST to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN) which affect activity of the monoaminergic cell groups in the midbrain (Li et al., 2023).

Literature reveals the involvement of VTA dopaminergic neurons in anxiety disorders (Hu, 2016; Morales and Margolis, 2017). The BNST strongly innervates the VTA, and 90% of BNST neurons projecting to the VTA have been identified as GABAergic/non-glutamatergic (Dong and Swanson, 2006a; Kudo et al., 2012; Kim et al., 2013). Moreover, the BNST also sends GABAergic projections to the DRN (Dong et al., 2001), and studies find that activation of serotonergic neurons in the DRN promotes reward and further participates in the regulation of anxiety (Luo et al., 2015). Our recent research finds that activation of avBNST GABAA receptors increases the mean firing rate of VTA dopaminergic neurons and DRN serotonergic neurons and produces anxiolytic-like behaviors in both sham and parkinsonian rats, indicating the involvement of avBNSTGABA–VTA and avBNSTGABA–DRN pathways in PD-related anxiety (Li et al., 2023). However, it is unclear whether the two pathways are respectively implicated in the regulation of PD-related anxiety and affect the release of monoaminergic transmitters in the basolateral amygdala (BLA). By using Gq/Gi coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and clozapine N-oxide (CNO) administration, the present series of experiments aimed to investigate the direct GABAergic projection from the avBNST to the VTA and effects of activation/inhibition of avBNSTGABA–VTA on anxiety-like behaviors and dopamine (DA) release in the BLA of sham and parkinsonian rats; the direct GABAergic projection from the avBNST to the DRN and effects of activation/inhibition of avBNSTGABA–DRN on anxiety-like behaviors and serotonin (5-HT) release in the BLA in the two groups of rats.