Altered c-Fos expression following alcohol intake in discrete brain regions of galanin 3 receptor knockout mice

The aim of this study was to investigate the brain regions involved in the role of galanin (GAL) and specifically GAL₃-receptors (GAL₃) in alcohol intake. GAL₃-KO mice displayed an alcohol-preferring phenotype in a two-bottle, free choice paradigm. In contrast, no genotype differences in ethanol intake were observed in a Drinking In the Dark (DID) model, highlighting the differential involvement of brain GAL activity depending on the experimental model of alcohol consumption. Blood ethanol concentrations were approximately 10 % lower in GAL₃-KO mice compared to wildtype (WT) following DID. WT mice drinking ethanol had significantly increased numbers of c-Fos immunoreactive (ir) neurons in the rostral prelimbic (PrL) and infralimbic (IL) regions of the prefrontal cortex (PFC) and decreased numbers of ir neurons in the CA1 region of the dorsal hippocampus (dHIP) compared to water drinking WT littermates, but these effects of ethanol were absent in GAL₃-KO mice. Water drinking GAL₃-KO mice furthermore had significantly increased numbers of c-Fos ir neurons compared to water drinking WT mice in the rostral PrL as well as the CA3 region of the dHIP. In the core and shell subregions of the nucleus accumbens (NAc), or in the paraventricular nucleus of the hypothalamus (PVN) or basolateral amygdala, there were no changes in the number of c-Fos ir cells or any involvement of GAL₃ genotype. These findings support a role of GAL₃-receptors in the effects of alcohol and implicate discrete brain regions involved in this interaction.