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1 Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia
2 Pain Management Research Institute, University of Sydney at the Royal North Shore Hospital, St Leonards, Sydney NSW, Australia
3 Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australia; Prince of Wales Medical Research Institute, University of New South Wales, Randwick, SYDNEY NSW, Australia
* To whom correspondence should be addressed. E-mail: p.osborne{at}usyd.edu.au.
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. As 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 if they are modulated by postsynaptic 5-HT receptors. Inward currents were predominantly induced by 5-HT in non-cholinergic 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 non-cholinergic neurons were blocked with cesium. Consistent with 5-HT7 receptor activation of h-curents via 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 striato-pallidal and cholinergic corticopetal circuitry in the ventral pallidum.
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