The neuropeptide galanin is implicated in regulation of affective behavior, including modulation of 5-HT signaling. Here, we investigated, by use of microdialysis in freely moving rats, the effects of intracerebral (i.c.) and intracerebroventricular (i.c.v.) infusions of galanin on basal extracellular 5-HT levels in medial prefrontal cortex (mPFC), CA1 area of ventral hippocampus (vHPC), central amygdaloid nucleus (CeA), ventromedial hypothalamic nucleus ventrolateral part (VMHvl), and ventromedial caudate putamen (CPu). These results were compared with a parallel immunohistochemical analysis of the distribution of galanin, 5-HT, and noradrenaline (NA) nerve terminals, and with data on galanin receptors. Galanin i.c.v. significantly decreased the 5-HT levels in mPFC to 79% and in vHPC to 72%. Local infusions of galanin caused a long-lasting decrease in 5-HT levels in vHPC to 88%, and a moderate decrease in CeA, whereas the 5-HT levels in mPFC significantly increased to 121%. These effects of i.c. galanin correlated well with the density of 5-HT and galanin nerve terminals and galanin receptors autoradiography in mPFC, vHPC, and CeA. No effects of i.c. or i.c.v. galanin on 5-HT levels were observed in CPu or VMHvl, in agreement with the low numbers of galanin-positive terminals and low/moderate galanin receptor density. Galanin was often found to coexist in NA, but could never be detected in 5-HT terminals. Together the results show a neuroanatomical correlation between the effects of galanin infusions on 5-HT release and distribution of galanin and its receptors, and that i.c.v. and i.c. administration can give opposite effects on 5-HT release. Synapse 68:179–193, 2014. © 2014 Wiley Periodicals, Inc.
Differential effects of intracerebroventricular (i.c.v.) and intracerebral (local) infusions of galanin on basal extracellular 5-HT levels in five selected regions of adult rat brain. Galanin-induced effects on 5-HT release correlated with strong to moderate density of galanin positive terminals in mPFC, vHPC, and CeA. Correspondingly, the lack of effect on 5-HT release correlated with moderate to low galanin fibre densities in VMHvl and CPu.