Opposing Electrophysiological Actions of 5-HT on Noncholinergic and Cholinergic Neurons in the Rat Ventral Pallidum in Vitro

The ventral pallidum in rat is a basal forebrain structure that contains neurons that project in the limbic striatopallidal circuitry and magnocellular cholinergic corticopetal neurons. Because 5-hydroxytryptamine (5-HT) terminals on dorsal raphe projections form close appositions with these neurons, we made patch-clamp recordings in immature rat brain slices to determine whether they are modulated by postsynaptic 5-HT receptors. Inward currents were predominantly induced by 5-HT in noncholinergic neurons, which were distinguished from cholinergic neurons by immunohistochemical and electrophysiological criteria. The inward current induced by 5-HT was mimicked and occluded when adenylyl cyclase was stimulated with forskolin, and was almost abolished when h-currents in noncholinergic neurons were blocked with cesium. Consistent with 5-HT(7) receptor activation of h-curents by cAMP in other brain regions, we found inward currents were mimicked by the mixed 5-HT(1)/5-HT(7) agonists 5-methoxytryptamine, and by 5-carboxamidotryptamine (5-CT), which was more potent than 5-HT. In contrast, 5-HT(1) preferring 8-OH-DPAT was a weak partial agonist, and the 5-HT(1)-selective antagonist pindolol had no effect. However, despite this profile, antagonists that bind at the 5-HT(7) receptor only partly reduced the agonist inward current (SB-269970 and clozapine), or had no effect (mianserin and pimozide). We found in cholinergic neurons that 5-HT predominantly induced hyperpolarizing currents, which were carried by potassium channels, and were smaller than currents induced by 8-OH-DPAT and 5-CT. We conclude from this study that ascending 5-HT projections from the dorsal raphe could have direct and opposite effects on the activities of neurons within the limbic striatopallidal and cholinergic corticopetal circuitry in the ventral pallidum.