Galanin-5-hydroxytryptamine interactions: electrophysiological, immunohistochemical and in situ hybridization studies on rat dorsal raphe neurons with a note on galanin R1 and R2 receptors.

摘要

Galaninergic mechanisms related to 5-hydroxytryptamine neurons in the dorsal raphe nucleus of the rat were analysed using electrophysiology, immunohistochemistry and in situ hybridization. Galanin caused a dose-dependent hyperpolarization accompanied by a decrease in membrane resistance in most 5-hydroxytryptamine-sensitive dorsal raphe neurons. The galanin-induced outward current reversed at about - 105 mV and shifted to a more positive potential with increasing extracellular potassium concentrations. The 5-hydroxytryptamine-induced outward current was enhanced and prolonged by preincubation with a low concentration of galanin (1-10 nM). The immunohistochemical analysis showed (i) generally low levels of galanin in the 5-hydroxytryptamine cell bodies, (ii) moderate numbers of galanin-positive nerve endings around the 5-hydroxytryptamine cell bodies, (iii) presence of galanin-like immunoreactivity in 5-hydroxytryptamine-positive dendrites and (iv) galanin-positive, 5-hydroxytryptamine-negative boutons making synaptic contact with 5-hydroxytryptamine-positive dendrites. The in situ hybridization results suggest that the galanin receptor present in the galanin/5-hydroxytryptamine neurons is not of the recently cloned galanin-R1 type. Taken together these results indicate that galanin exerts an inhibitory effect via an increase in K+ conductance in 5-hydroxytryptamine neurons by acting on a postsynaptic receptor. In addition, galanin at low, possibly physiological concentrations enhances the inhibitory effect of 5-hydroxytryptamine at the cell soma level. We propose that galanin primarily is released from adjacent galanin boutons lacking 5-hydroxytryptamine and also from soma and dendrites of galanin/5-hydroxytryptamine dorsal raphe neurons. Galanin may thus be involved in the manifold functions hitherto ascribed to ascending 5-hydroxytryptamine neurons, for example in mood regulation.