Galanin Modulates 5‐Hydroxytryptamine Functions: Focus on Galanin and Galanin Fragment/5‐Hydroxytryptamine 1A Receptor Interactions in the Brain a

A bstract : The reciprocal interactions between galanin and 5‐HT 1A receptors in the rat brain are presented. Galanin and its NH 2 ‐terminal fragments antagonize 5‐HT 1A receptor‐mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5‐HT1A receptor activation at the soma‐dendritic level, leading to reductions of 5‐HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of antidepressant drug, based on the 5‐HT hypothesis of depression, by enhancing 5‐HT release and postjunctional 5‐HT 1A ‐mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY‐immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.