AbstractÐGalanin is widely distributed throughout the mammalian brain and has been implicated in the regulation of food intake, metabolism and reproductionÐfunctions that are also thought to be under the control of leptin. To investigate the possible role of galanin in mediating the physiological effects of leptin in the mouse, we had three experimental objectives: ®rst, to map the distribution of galanin messenger RNA-expressing cells in the brain of the mouse; second, to assess the effects of leptin on galanin gene expression in areas of the brain thought to be involved in the regulation of body weight and reproduction; and third, to determine whether galanin neurons in these regions express leptin receptor messenger RNA. We found the pattern of galanin messenger RNA expression in the mouse brain to be similar, but not identical, to that in the rat. Leptin treatment (2 mg/g for six days) signi®cantly reduced cellular levels of galanin messenger RNA in the hypothalamic periventricular nucleus of leptin-de®cient obese (ob/ob) mice (P , 0.01) by approximately 30%; however, leptin did not appear to in¯uence the expression of galanin in the arcuate or dorsomedial nucleus of the hypothalamus. Galanin-producing neurons in the arcuate, dorsomedial and periventricular nuclei did not appear to express leptin receptor messenger RNA (P . 0.05).These results demonstrate that galanin distribution patterns in the mouse brain are comparable to other species and, yet, possess unique features. In addition, galanin-expressing neurons in the hypothalamic periventricular nucleus are targets for regulation by leptin; however, the effect of leptin on galanin gene expression is likely to be mediated indirectly, perhaps through either proopiomelanocortin-or neuropeptide Y-expressing cells in the hypothalamus. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: neuropeptide, gene regulation, neuroanatomy, in situ hybridization, leptin receptor.Galanin is a 29 amino acid neuropeptide that was originally isolated from the porcine gut. 42 In mammals, galanin is widely distributed throughout the central and peripheral nervous systems. 26 One curious observation about galanin's expression in the brain of mammals is its species speci®city, which is particularly evident in the rat and monkey. For example, in the rat there is little or no expression of galanin in the hippocampus but there are abundant galanin-containing cells in the dorsal raphe. 23,34 In the monkey, however, galanin producing cells are found throughout the hippocampus, yet are absent from the dorsal raphe. 17 To date, there has been no detailed mapping of the distribution of galanin in the mouse brain. Because of the growing importance of the mouse as a genetic model for understanding the brain, it is vital that we know the comparative anatomy of neuropeptide expression in the murine brain and use this information to shed light on the differences and similarities between species. The ®rst objective of this study was to complete a detailed map of the...