[125I]-Galanin binding in brain of wildtype, and galanin- and GalR1-knockout mice: Strain and species differences in GalR1 density and distribution

Widespread production of knockout and transgenic mice has led to an increased use of mice as animal models for studies of normal- and patho-physiology. Hence, the precise mapping of central transmitter/peptide systems in the mouse has become essential for the interpretation of functional studies and for the correct correlation with findings obtained in the rat, primates and/or human. In this regard, the current study reports the autoradiographic localization of [125I]-galanin (GAL) binding sites in brain of the common C57BL/6J and 129OlaHsd mouse strains, as well as in GAL and galanin receptor-1 (GalR1) knockout (KO) mice. In C57BL/6J and 129OlaHsd mice, [125I]-GAL binding sites were detected throughout the brain, including moderate-high relative densities in the basal ganglia (caudate putamen, nucleus [n.] accumbens, olfactory tubercle, substantia nigra), limbic regions (septum, bed n. stria terminalis, ventral hippocampus, amygdala), cingulate, retrosplenial, entorhinal cortex, centro-lateral/medial thalamic n., preoptic/lateral hypothalamus, midbrain (superior colliculus, periaqueductal gray), pons/medulla oblongata (parabrachial, pontine reticular and solitary tract n.) and cerebellar cortex. [125I]-GAL binding levels were low or absent in main olfactory bulb, neocortex, ventrolateral/geniculate thalamic n., dorsal hippocampus, inferior colliculus and cranial motor n. In simultaneous determinations, relative [125I]-GAL binding site densities in brain were generally lower in C57BL/6J than in 129OlaHsd mice, while the density and distribution of central binding in the GAL-KO mouse was essentially identical to that in its background-129OlaHsd strain. In contrast, no specific [125I]-GAL binding was detected in any region of GalR1-KO mouse brain, revealing that under the experimental conditions used, the peptide ligand binding is predominantly (exclusively) to the GalR1 subtype. This evaluation of GAL receptor site distribution in mouse brain has revealed similarities and some differences with the equivalent system in rat and provides a valuable reference for future comparative studies of central GAL transmission.