PRESYNAPTIC NICOTINIC RECEPTORS FACILITATE MONOAMINERGIC TRANSMISSION

Nicotine is reported to increase arousal and attention and to elevate mood, effects that are most often associated with changes in the funct ion of monoaminergic neuromodulatory systems (Feldman et al., 1997). R ecent studies have shown a nicotinic receptor-mediated presynaptic enh ancement of fast glutamatergic (McGehee et al., 1995; Gray et al., 199 6) and GABAergic (Lena and Changeux, 1997) transmission. However, the mechanism of nicotinic effects on metabotropic-mediated transmission i n general, and on monoaminergic transmission in particular, is less we ll understood. We have examined nicotinic effects on dorsal raphe neur ons of rats using whole-cell current and voltage-clamp recording techn iques in vitro. In the majority of these neurons, activation of presyn aptic nicotinic receptors induced a depolarization mediated by norepin ephrine acting on alpha 1 receptors. Blockade of this response reveale d a hyperpolarization mediated by serotonin acting on 5-HT1A receptors . Because the norepinephrine effect was sensitive to methyllycaconitin e (100 nM), it is concluded that nicotinic receptors with an alpha 7 s ubunit can facilitate release of norepinephrine to activate metabotrop ic receptors. In contrast, methyllycaconitine-insensitive nicotinic re ceptors can induce 5-HT release in the dorsal raphe nucleus.