Species and sex differences in brain distribution of corticotropin- releasing factor receptor subtypes 1 and 2 in monogamous and promiscuous vole species

Corticotropin-releasing factor (CRF) receptor subtypes 1 and 2 have been implicated in rodent models of anxiety, but much less is known about the CRF system and social behavior. Both corticosterone and central CRF receptors modulate pair bonding in the monogamous prairie vole. Using receptor autoradiography, we mapped CRFR₁ and CRFR₂ in the brains of two monogamous vole species, the prairie vole and pine vole, and two promiscuous vole species, the meadow vole and montane vole. We found markedly different patterns of brain CRFR₁ and CRFR₂ binding among the four species, including species differences in the olfactory bulb, nucleus accumbens, lateral septum, hippocampus, laterodorsal thalamus, cingulate cortex, superior colliculus, and dorsal raphe. Interestingly, we also observed striking sex differences in voles: CRFR₂ binding was higher in the encapsulated bed nucleus of the stria terminalis in males than females for all four vole species. These results suggest possible sites of action for CRF-induced facilitation of pair bond formation in prairie voles, as well as potential sex differences in the CRF modulation of pair bonding. Further examination of CRF receptors in vole species may reveal a novel role for CRF in social behavior. Ultimately, our results identify several brain regions with conserved CRF receptor patterns across rodent and primate species, in contrast to several brain regions with phylogenetically plastic CRF receptor patterns, and have interesting implications for the evolution of CRF receptor patterns and behavior.