Electrophysiological characterization of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra.
The electrophysiological characteristics of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra was investigated using the whole-cell patch clamp technique under the voltage-clamp mode. Nicotine (0.01 - 100 microM) induced inward currents corresponding to nicotine-induced depolarization with an increase in firing in a dose-dependent manner. This current was inhibited by dihydro-beta-erythroidine, a selective antagonist for the alpha4beta2 type neuronal nicotinic receptor. Nicotine directly acts on postsynaptic alpha4beta2 type nicotinic receptors and induces inward currents, resulting in excitation of dopaminergic neurons in the substantia nigra and subsequent enhancement of dopamine release in the corpus striatum.
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
Hiroaki
H
Matsubayashi
Taku
T
Amano
Takahiro
T
Seki
Masashi
M
Sasa
Norio
N
Sakai
D000818:Animals; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D017981:Receptors, Neurotransmitter; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D004298:Dopamine