Corticotropin-releasing factor receptors in the rabbit brain visualized by in vitro autoradiography

Abstract

Corticotropin-releasing factor (CRF) binding sites were visualized in the rabbit brain by in vitro autoradiography using the radioligand 125I-[Tyr 0]ovine CRF. The radioligand binding to sections of rabbit cingulate cortex were competed for by ovine and rat CRF with inhibitory constants (K i) of 26 and 37 nM, respectively, whereas sauvagine and alpha-helical CRF 9–41 were approximately 10-fold less potent. In the rabbit brain, the highest densities of binding sites for CRF are found in the pineal gland and the choroid plexus. The cerebral cortex is labelled throughout, with the highest concentration of binding sites in the piriform and primary olfactory divisions. In the cerebellar cortex, the granular layer is more intensely labelled than the molecular layer. The distribution of CRF binding sites in the hippocampus follows a laminar pattern; the molecular layer of the dentate gyrus is intensely labelled, the oriens, radiatum and lacunosum moleculare layers of Ammon's horn contain moderate densities of binding and no binding is observed in the granular layer of the dentate gyrus and the pyramidal cell layer. The ventral subnucleus of the lateral septum, the zonal and superficial layers of the superior colliculus contain high densities of receptors. A moderate concentration of binding sites is observed in the caudate nucleus, putamen, bed nucleus of the stria terminalis, paraventricular, anterodorsal and anteroventral thalamic nuclei and the medial nucleus of the mammillary body. The fundus striati, the dorsal subnucleus of the lateral septum, the lateral dorsal thalamic, lateral and medial geniculate nuclei, the lateral and anterior cortical amygdaloid nuclei, central and posterior interpeduncular nuclei all contain low but significant levels of CRF binding sites. No detectable binding is observed in the pons, medulla oblongata or fibre tracts. The high densities of CRF binding sites found in the cortex, hippocampus and structures associated with the limbic system supports a role for CRF in the modulation of behavioural and physiological responses associated with stress. However, the extremely high density of CRF binding sites found in the pineal gland and choroid plexus suggest a more extensive role for CRF in the rabbit central nervous system.