Calcitonin gene-related peptide (hCGRPα) binding sites in the nucleus accumbens. Atypical structural requirements and marked phylogenic differences

Abstract

The distribution of [ 125I]hCGRPα binding sites was studied in tissue sections from rat brain and, at the level of the nucleus accumbens in the brains of 6 other species. In the rat, very high levels of binding were found in the nucleus accumbens, the amygdaloid complex and mammillary body while high amounts were localized to the superficial layers of the superior colliculus, temporal cortex, cerebellum (molecular layer), frontal cortex and inferior olive. Moderate densities of [ 125I]hCGRPα binding were observed in the medial geniculate nucleus, inferior colliculus and substantia nigra. Regional competition studies in rat brain showed that salmon calcitonin was almost as effective as hCGRPα in competing for [ 125I]hCGRPα binding sites in the nucleus accumbens but was mostly inactive in other regions such as the mesolimbic cortex and the striatum. On the basis of their atypical sensitivity to salmon calcitonin, [ 125I]hCGRPα binding sites in the rat nucleus accumbens, which appear between postnatal days 4 and 7, do not seem to correspond to either the CGRP 1 or CGRP 2 receptor subtypes 6. Marked species differences were observed in the distribution of [ 125I]hCGRPα binding sites, especially in the nucleus accumbens. In the mouse, low densities of hCGRPα sites were observed in striatum and fronto-parietal cortex while low to moderate levels were found in the medial and posterior aspects of the nucleus accumbens. A similar distribution was seen in the guinea pig brain albeit of generally higher density. In the rat, very high amounts of [ 125I]hCGRPα binding were seen in the nucleus accumbens while lower levels were found in the striatum and certain cortical areas. In the rabbit, a very high density of [ 125I]hCGRPα labelling was observed in the nucleus accumbens, caudate nucleus and putamen, whereas low levels were present in the cortex. A very high density of [ 125I]hCGRPα binding sites were localized throughout the basal ganglia and the cortical ribbon of pig brain. Finally, in both monkey and human brain, only low densities of binding sites were seen in the nucleus accumbens and surrounding structures. Thus, it seems that the appearance of [ 125I]hCGRPα binding sites in the nucleus accumbens, of unique pharmacological profile in the rat, is highly species dependent.