The α1 and γ2 subunit-containing GABAA receptor-mediated inhibitory transmission in the anteroventral bed nucleus of stria terminalis is involved in the regulation of anxiety in rats with substantia nigra lesions

Abstract

The anteroventral bed nucleus of the stria terminalis (avBNST) is widely acknowledged as a key brain structure that regulates negative emotional states, such as anxiety. At present, it is still unclear whether GABA_A receptor-mediated inhibitory transmission in the avBNST is involved in Parkinson's disease (PD)-related anxiety. In this study, unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (SNc) in rats induced anxiety-like behaviors, increased GABA synthesis and release, and upregulated expression of GABA_A receptor subunits in the avBNST, as well as decreased level of dopamine (DA) in the basolateral amygdala (BLA). In both sham and 6-OHDA rats, intra-avBNST injection of GABA_A receptor agonist muscimol induced the following changes: (i) anxiolytic-like responses, (ii) inhibition of the firing activity of GABAergic neurons in the avBNST, (iii) excitation of dopaminergic neurons in the ventral tegmental area (VTA) and serotonergic neurons in the dorsal raphe nucleus (DRN), and (iv) increase of DA and 5-HT release in the BLA, whereas antagonist bicuculline induced the opposite effects. Collectively, these findings suggest that degeneration of the nigrostriatal pathway enhances GABA_A receptor-mediated inhibitory transmission in the avBNST, which is involved in PD-related anxiety. Further, activation and blockade of avBNST GABA_A receptors affect the firing activity of VTA dopaminergic and DRN serotonergic neurons, and then change release of BLA DA and 5-HT, thereby regulating anxiety-like behaviors.

Keywords: Anxiety; Bed nucleus of stria terminalis; Dopamine; GABA(A) receptor; Parkinson's disease; Serotonin.