The antidepressant-like effect of galanin in the dorsal raphe nucleus of rats involves GAL2 receptors.

Galanin is a neuropeptide distributed in human and rat brain regions that are involved with emotional regulation, such as the dorsal raphe nucleus (DRN). Galanin effects in the DRN are mediated by GAL1 and GAL2 receptors. Intracerebral infusion of a GAL2 (AR-M1896) or a GAL1 (M617) agonist induced either antidepressant or depressive-like effect, respectively, in rats exposed to the forced swimming test (FST). However, it is not clear if GAL1 and/or GAL2 receptors present in the DRN would be involved in such effects. Therefore, we investigated the effects induced by intra-DRN infusion of galanin (0.3 nmol), AR-M1896 (1 nmol, GAL2 agonist), or M617 (GAL1 agonist) in rats exposed to the FST. Galanin and AR-M1896 intra-DRN administration induced antidepressant-like effect in the FST. However, M617 did not induce any change in the FST. Neither M617 nor AR-M1896 changed the locomotor activity of rats in the open field test. Intra-DRN pre-treatment with M871 (1 nmol), a selective GAL2 antagonist, counteracted the antidepressant-like effect induced by galanin. These results suggest that galanin signaling through GAL2 receptors in the DRN produces triggers antidepressant-like effect.

Infusion of galanin into the mid-caudal portion of the dorsal raphe nucleus has an anxiolytic effect on rats in the elevated T-maze.

Galanin and 5-HT coexist in dorsal raphe nucleus (DRN) neurons. Microinjection of galanin into the DRN reduces the firing rate of serotonin neurons. Serotonergic neurons projecting from the DRN to the amygdala facilitate learned anxiety producing an anxiogenic effect, while those projecting from the periaqueductal grey affect innate anxiety producing a panicolytic effect. We tested the hypothesis that injection of galanin into rat DRN would induce anxiolytic/panicogenic effects in the elevated T-maze (ETM), a model that allows for the evaluation of both of these effects. Galanin infusion into the mid-caudal DRN, but not into the rostral DRN, impaired inhibitory avoidance, suggesting an anxiolytic effect. The effective dose of galanin (0.3 nmol) did not modify locomotor activity in the open field. Contrary to expectations, microinjection of galanin into the DRN did not facilitate the latency of one-way escape in the ETM. Pretreatment with a galanin antagonist, M40, attenuated galanin-induced impairment of inhibitory avoidance. The results show that microinjection of a low dose of galanin only into the mid-caudal DRN has an anxiolytic effect. This effect seems to be mediated, at least in part, by galanin receptors. Further investigation is necessary to identify the receptor subtypes and the DRN subregion involved in the anxiolytic effect of galanin.