Presynaptic Nicotinic Receptors Facilitate Monoaminergic Transmission

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Abstract
Nicotine is reported to increase arousal and attention and to elevate mood, effects that are most often associated with changes in the function of monoaminergic neuromodulatory systems (Feldman et al., 1997). Recent studies have shown a nicotinic receptor-mediated presynaptic enhancement of fast glutamatergic (McGehee et al., 1995;Gray et al., 1996) and GABAergic (Léna and Changeux, 1997) transmission. However, the mechanism of nicotinic effects on metabotropic-mediated transmission in general, and on monoaminergic transmission in particular, is less well understood. We have examined nicotinic effects on dorsal raphe neurons of rats using whole-cell current and voltage-clamp recording techniquesin vitro. In the majority of these neurons, activation of presynaptic nicotinic receptors induced a depolarization mediated by norepinephrine acting on α1 receptors. Blockade of this response revealed a hyperpolarization mediated by serotonin acting on 5-HT1Areceptors. Because the norepinephrine effect was sensitive to methyllycaconitine (100 nm), it is concluded that nicotinic receptors with an α7 subunit can facilitate release of norepinephrine to activate metabotropic receptors. In contrast, methyllycaconitine-insensitive nicotinic receptors can induce 5-HT release in the dorsal raphe nucleus.