| Title | Activation of AMPA Receptors in the Lateral Habenula Produces Anxiolytic Effects in a Rat Model of Parkinson's Disease |
| Authors | Zhang, Jin Wang, Xiaobing Bernardi, Rick E. Ju, Jun Wei, Shoupeng Gong, Zhiting |
| Affiliation | Peking Univ, Shenzhen Grad Sch, Guangdong Prov Key Lab Chem Gen, State Key Lab Chem Oncogen, Shenzhen, Peoples R China Dali Univ, Coll Preclin Med, Dept Anat, Dali, Peoples R China Cent Inst Mental Hlth, Inst Psychopharmacol, Med Fac Mannheim, Heidelberg, Germany Southern Univ Sci & Technol, Brain Res Ctr, Shenzhen, Peoples R China Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China Sun Yat Sen Univ, Affiliated Hosp 7, Precis Med Res Ctr, Tomas Lindahl Nobel Laureate Lab, Shenzhen, Peoples R China |
| Keywords | VENTRAL TEGMENTAL AREA BASOLATERAL AMYGDALA INHIBITORY TRANSMISSION ANXIETY RESPONSES 5-HT1A RECEPTORS NUCLEUS NEURONS GLUTAMATE BEHAVIORS COMPLEX |
| Issue Date | 25-Jan-2022 |
| Publisher | FRONTIERS IN PHARMACOLOGY |
| Abstract | Background: Parkinson's disease (PD) is commonly accompanied with anxiety disorder, 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 (AMPARs). The PD model for the pharmacological intervention of AMPA receptors was established by the unilateral lesion of the substantia nigra pars compacta (SNc) with 6-hydroxydopamine (6-OHDA).Methods: The AMPAR agonist (S)-AMPA and antagonist NBQX were microinjected into the LHb, respectively, to examine whether anxiety-like behaviors were altered in sham-operated and SNc-lesion rats, measured with the paradigms of 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 enhanced the extracellular DA and 5-HT in the BLA. Conversely, NBQX induced anxiety-like effects and suppressed the extracellular DA and 5-HT in the BLA. In addition, the minimal doses inducing the effects in the SNc-lesion rats were lower than those in sham-operated rats.Conclusion: These findings suggest that the effects of AMPA receptors in the LHb on anxiety-like behaviors likely involve the extracellular levels of DA and 5-HT in the BLA. The present results may improve our understanding of the neuropathology and/or treatment of PD. |
| URI | http://hdl.handle.net/20.500.11897/637811 |
| DOI | 10.3389/fphar.2022.821975 |
| Indexed | SCI(E) |
| Appears in Collections: | 深圳研究生院待认领 |
