Excitation of rat striatal large neurons by dopamine and/or glutamate released from nerve terminals via presynaptic nicotinic receptor (alpha(4)beta(2) type) stimulation

Previous in vivo experiments using rats anesthetized with chloral hydrate h ave revealed that nicotine applied iontophoretically increased firing of st riatal neurons receiving excitatory dopaminergic input from the substantia nigra, and nicotine-induced firing was inhibited by domperidone, a dopamine D-2 antagonist. The results suggest that nicotine increases release of dop amine from the terminals of dopaminergic neurons. Therefore, we performed t he present patch clamp study using slice and acutely dissociated preparatio ns of the rat striatum to elucidate the mechanisms underlying the nicotine- induced excitation of striatal neurons. Application of nicotine (100 uM) to large striatal neurons in slice preparations did not produce any effect on the resting membrane potential, but did increase the frequency of miniatur e postsynaptic potentials (mpps) and action potentials in all 15 neurons te sted. The nicotine-induced increase in mpps and action potentials were inhi bited during simultaneous application of domperidone; L-glutamic acid dieth yl ester hydrochloride, a non-selective glutamate receptor antagonist; and/ or dihydro-beta -erythroidine, a central nicotinic acetylcholine receptor ( alpha (4)beta (2) 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 suc h as dopamine and/or glutamate, thereby activating the striatal large neuro ns.