Comparative analysis of the central CCK system in Fawn Hooded and Wistar Kyoto rats: Extended localisation of CCK-A receptors throughout the rat brain using a novel radioligand

The neuropeptide cholecystokinin has been implicated in the actions of a number of central processes including anxiety and reward. For this reason, the aim of the present study was to compare the density of CCK-A and -B receptors and the mRNA encoding preproCCK throughout the brains of an alcohol-preferring (Fawn Hooded) rat strain with that of a non-alcohol-preferring (Wistar Kyoto) strain of rat. Our study revealed significant differences with regard to the central CCK system of the FH compared to the WKY rat, including differences in CCK-A receptor binding throughout the dorsal medulla, and altered CCK-B binding density throughout the cerebral cortex and reticular nucleus of the thalamus. The most striking result, given the altered behavioural phenotype of the FH rat, was the 33% lower density of CCKmRNA measured throughout the ventral tegmental area of the FH rat when compared to the WKY. This study also reports on a protocol to utilise a novel radioligand, [¹²⁵I]-D-Tyr-Gly-A-71378, for autoradiographic detection of CCK-A receptors throughout the rat brain. As previously reported, CCK-A receptors were located throughout the area postrema, interpeduncular nucleus and nucleus tractus solitarii; however, binding to CCK-A receptors was also visualised throughout the medial pre-optic area, the arcuate nucleus and the circumventricular regions of the ventral hypothalamus, regions known to contain CCK-A receptors but which were previously undetectable using autoradiography in rat brain.