AUTHOR=Zhang Jin , Wang Xiaobing , Bernardi Rick E. , Ju Jun , Wei Shoupeng , Gong Zhiting 

TITLE=Activation of AMPA Receptors in the Lateral Habenula Produces Anxiolytic Effects in a Rat Model of Parkinson’s Disease

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.821975

DOI=10.3389/fphar.2022.821975

ISSN=1663-9812

ABSTRACT=Background Anxiety is a common symptom in Parkinson’s disease (PD), however, the mechanisms underlying PD-mediated anxiety remain elusive. The lateral habenula (LHb) is a critical brain region that influences the activity of the monoaminergic system in the midbrain and consequently modulates anxiety. Most neurons in the LHb express AMPA receptors. We performed the unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra pars compacta (SNc) to establish the PD model for the pharmacological intervention of AMPA receptors. 
Methods The AMPA receptor agonist (S)-AMPA and antagonist NBQX were microinjected into the LHb to examine whether anxiety-like behaviors were altered in sham-operated rats and SNc-lesioned rats as measured using the open-field test (OPT) and elevated plus maze (EPM). Furthermore, dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the basolateral amygdala (BLA) were measured using in vivo microdialysis immediately following the injections of (S)-AMPA and NBQX into the LHb. 
Results Activation of LHb AMPA receptors by (S)-AMPA produced anxiolytic-like behaviors and increased extracellular DA and 5-HT in the BLA. Conversely, NBQX induced anxiety-like effects and decreased extracellular DA and 5-HT in the BLA. 
Conclusions These findings suggest that the effects of AMPA receptors in the LHb on anxiety-like behaviors likely involve extracellular levels of DA and 5-HT in the BLA. The present results may have implications for improving our understanding of the neuropathology and/or treatment of PD.