Functional role of nicotinic receptor in striato-nigral dopaminergic pathway using patch clamp method.

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In this study, I tried to investigate the functional role of nicotinic acetylcholine receptor in the stiato-nigral dopaminergic system using patch clamp method. Previous in vivo experiments using rats anesthetized with chloral hydrate have revealed that nicotine applied iontophoretically increased firing of striatal neurons receiving exicitatory dopaminergic input from the substantia nigra, and nicotine-induced firing was inhibited by domperidone. Therefore, I performed the patch-clamp study using slice preparations of the rat striatum to elucidate the mechanisms underlying nicotine-induced excitation of striatal neurons. Application of nicotine to the bath did not produce any effect on the resting membrane potential, but did increase the frequency of miniature postsynaptic potentials. Domperidone (a dopamine D2 receptor antagonist) and/or GDEE (a non-selective glutamate receptor antagonist) inhibited this excitatory effect of nicotine. These results suggest that nicotine acts on the nerve terminals to release neurotransmitters such as dopamine and/or glutamate, thereby activating the striatal neurons.On the other hand, a patch-clamp study using slice preparations of the substantia nigra revealed that nicotine induced a dose-dependent depolarization of dopaminergic neurons accompanying by an increase in firing. The nicotine-induced depolarization was observed even in a Ca^<2+>-free / high Mg^<2+> solution. These results suggest that nicotine postsynaptically activates dopaminergic neurons in the substantia nigra to facilitate dopamine release in the striatum beside eliciting presynaptic effects on the dopaminergic terminals.