Distinctive Nicotinic Acetylcholine Receptor Functional Phenotypes Of Rat Ventral Tegmental Area Dopaminergic Neurons
Department
neurobiology
Document Type
Article
Abstract
Dopaminergic (DAergic) neuronal activity in the ventral tegmental area (VTA) is thought to contribute generally to pleasure, reward, and drug reinforcement and has been implicated in nicotine dependence. nAChRs expressed in the VTA exhibit diverse subunit compositions, but the functional and pharmacological properties are largely unknown. Here, using patch-clamp recordings in single DAergic neurons freshly dissociated from rat VTA, we clarified three functional subtypes of nAChRs (termed ID, IID and IIID receptors) based on whole-cell current kinetics and pharmacology. Kinetic analysis demonstrated that comparing to ID, IID receptor-mediated current had faster activation and decay constant and IIID receptor-mediated current had larger current density. Pharmacologically, ID receptor-mediated current was sensitive to the α4β2-nAChR agonist RJR-2403 and antagonist dihydro-β-erythroidine (DHβE); IID receptor-mediated current was sensitive to the selective α7-nAChR agonist choline and antagonist methyllycaconitine (MLA); while IIID receptor-mediated current was sensitive to the β4-containing nAChR agonist cytisine and antagonist mecamylamine (MEC). The agonist concentration-response relationships demonstrated that IID receptor-mediated current exhibited the highest EC50 value compared to ID and IIID receptors, suggesting a relatively low agonist affinity of type IID receptors. These results suggest that the type ID, IID and IIID nAChR-mediated currents are predominately mediated by activation of α4β2-nAChR, α7-nAChR and a novel nAChR subtype(s), respectively. Collectively, these findings indicate that the VTA DAergic neurons express diversity and multiplicity of functional nAChR subtypes. Interestingly, each DAergic neuron predominantly expresses only one particularly functional nAChR subtype, which may have distinct but important roles in regulation of VTA DA neuronal function, DA transmission and nicotine dependence. © 2009 The Author. Journal compilation © 2009 The Physiological Society.
Publication Date
1-15-2009
Publication Title
Journal of Physiology
ISSN
00223751
Volume
587
Issue
2
First Page
345
Last Page
361
Digital Object Identifier (DOI)
10.1113/jphysiol.2008.162743
Recommended Citation
Yang, Kechun; Hu, Jun; Lucero, Linda; Liu, Qiang; Zheng, Chao; Zhen, Xuechu; Jin, Guozhang; Lukas, Ronald J.; and Wu, Jie, "Distinctive Nicotinic Acetylcholine Receptor Functional Phenotypes Of Rat Ventral Tegmental Area Dopaminergic Neurons" (2009). Translational Neuroscience. 139.
https://scholar.barrowneuro.org/neurobiology/139