Excitation of rat striatal large neurons by dopamine and/or glutamate released from nerve terminals via presynaptic nicotinic receptor (A4beta2 type) stimulation.
Previous in vivo experiments using rats anesthetized with chloral hydrate have revealed that nicotine applied iontophoretically increased firing of striatal neurons receiving excitatory dopaminergic input from the substantia nigra, and nicotine-induced firing was inhibited by domperidone, a dopamine D2 antagonist. The results suggest that nicotine increases release of dopamine from the terminals of dopaminergic neurons. Therefore, we performed the present patch clamp study using slice and acutely dissociated preparations of the rat striatum to elucidate the mechanisms underlying the nicotine-induced excitation of striatal neurons. Application of nicotine (100 microM) to large striatal neurons in slice preparations did not produce any effect on the resting membrane potential, but did increase the frequency of miniature postsynaptic potentials (mpps) and action potentials in all 15 neurons tested. The nicotine-induced increase in mpps and action potentials were inhibited during simultaneous application of domperidone; L-glutamic acid diethyl ester hydrochloride, a non-selective glutamate receptor antagonist; and/or dihydro-beta-erythroidine, a central nicotinic acetylcholine receptor (alpha4beta2 type) antagonist. Postsynaptic current was not induced by nicotine applied by U-tube in 96% of acutely dissociated striatal neurons. The present findings suggest that nicotine mainly acts on the presynaptic nicotinic receptors in the nerve terminals to release neurotransmitters such as dopamine and/or glutamate, thereby activating the striatal large neurons.
Matsubayashi
H
H
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Amano
T
T
Amano
H
H
Sasa
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010477:Perfusion; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D013268:Stimulation, Chemical
D018492:Dopamine Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; C403531:nicotinic receptor alpha4beta2; D018698:Glutamic Acid; D004294:Domperidone; D009538:Nicotine; D004298:Dopamine