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-HT7 receptor activation of h-curents by cAMP in other brain regions, we found inward currents were mimicked by the mixed 5-HT1/5-HT7 agonists 5-methoxytryptamine, and by 5-carboxamidotryptamine (5-CT), which was more potent than 5-HT. In contrast, 5-HT1 preferring 8-OH-DPAT was a weak partial agonist, and the 5-HT1–selective antagonist pindolol had no effect. However, despite this profile, antagonists that bind at the 5-HT7 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.
Comparison of the Novel Antipsychotic Ziprasidone with Clozapine and Olanzapine Inhibition of Dorsal Raphe Cell Firing and the Role of 5-HT1A Receptor Activation
