The avBNSTGABA-VTA and avBNSTGABA-DRN pathways are respectively involved in the regulation of anxiety-like behaviors in parkinsonian rats

Abstract

The anteroventral bed nucleus of stria terminalis (avBNST) is a key brain region which involves negative emotional states, such as anxiety. The most neurons in the avBNST are GABAergic, and it sends GABAergic projections to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN), respectively. The VTA and DRN contain dopaminergic and serotonergic cell groups in the midbrain which regulate anxiety-like behaviors. However, it is unclear the role of GABAergic projections from the avBNST to the VTA and the DRN in the regulation of anxiety-like behaviors, particularly in Parkinson's disease (PD)-related anxiety. In the present study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, and decreased level of dopamine (DA) in the basolateral amygdala (BLA). Chemogenetic activation of avBNST^GABA-VTA or avBNST^GABA-DRN pathway induced anxiety-like behaviors and decreased DA or 5-HT release in the BLA in sham and 6-OHDA rats, while inhibition of avBNST^GABA-VTA or avBNST^GABA-DRN pathway produced anxiolytic-like effects and increased level of DA or 5-HT in the BLA. These findings suggest that avBNST inhibitory projections directly regulate dopaminergic neurons in the VTA and serotonergic neurons in the DRN, and the avBNST^GABA-VTA and avBNST^GABA-DRN pathways respectively exert impacts on PD-related anxiety-like behaviors.

Keywords: Anxiety; Bed nucleus of stria terminalis; Dorsal raphe nucleus; Parkinson's disease; Ventral tegmental area.