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Comparative Study
. 2005 Jun 20;487(1):75-92.
doi: 10.1002/cne.20532.

Species and Sex Differences in Brain Distribution of Corticotropin-Releasing Factor Receptor Subtypes 1 and 2 in Monogamous and Promiscuous Vole Species

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Free PMC article
Comparative Study

Species and Sex Differences in Brain Distribution of Corticotropin-Releasing Factor Receptor Subtypes 1 and 2 in Monogamous and Promiscuous Vole Species

Miranda M Lim et al. J Comp Neurol. .
Free PMC article

Abstract

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 CRFR(1) and CRFR(2) 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 CRFR(1) and CRFR(2) 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: CRFR(2) 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.

Figures

Fig. 1
Fig. 1
Validation of CRF receptor autoradiography technique. A: Meadow vole brain section incubated with [125I-Tyr0]-sauvagine, which labels both CRFR1 and CRFR2. B: Prairie vole brain section incubated with [125I-Tyr0]-sauvagine. C: Meadow vole brain section incubated with [125I-Tyr0]-sauvagine plus the CRFR1 selective inhibitor CP-154,526, which ultimately labels only CRFR2. D: Prairie vole brain section labeling for CRFR2. E: Meadow vole brain section incubated with [125I-Tyr0]-sauvagine plus cold sauvagine, ultimately showing the nonspecific binding. F: Prairie vole brain section showing nonspecific binding. Scale bar = 1 mm in F (applies to A–F).
Fig. 2
Fig. 2
Total CRF receptor binding, highlighting differences in CRFR1 between promiscuous meadow and monogamous prairie vole species. Meadow vole (B) and prairie vole (C) brain sections through the olfactory bulb. Meadow vole (E) and prairie vole (F) brain sections through the nucleus accumbens. Note the strikingly dense CRFR1 binding in the shell of the NAcc in the meadow vole. Meadow vole (H) and prairie vole (I) brain sections showing the species difference in CRFR1 binding in the medial habenula nucleus. Note that the species difference in CRFR1 in the medial habenula is in the opposite direction as the species difference in the shell of the NAcc. Meadow vole (K) and prairie vole (L) hindbrain section highlighting the superior colliculus. Acetylcholinesterase-stained adjacent sections are shown to the left of each panel. Scale bars = 1 mm in C (applies to A,B,C), L (applies to D–L).
Fig. 3
Fig. 3
CRFR2 binding in promiscuous meadow and monogamous prairie vole species. Meadow vole (B) and prairie vole (C) sections through the striatum. Meadow vole (E) and prairie vole (F) brain sections through the lateral septum. Note that the species difference in CRFR2 in the lateral septum is in the opposite direction as the species difference in the striatum. Meadow vole (H) and prairie vole (I) brain sections through the hippocampus. Note the dense labeling in the CA1 fields. Meadow vole (K) and prairie vole (L) hindbrain sections through the principal nucleus of five. Acetylcholinesterase-stained adjacent sections are shown to the left of each panel. Scale bar = 1 mm in L (applies to A–L).
Fig. 4
Fig. 4
Total CRF receptor binding, highlighting differences in CRFR1 between promiscuous montane and monogamous pine vole species. Montane vole (B) and pine vole (C) brain sections through the olfactory bulb. Montane vole (E) and pine vole (F) brain sections through the nucleus accumbens. Note the strikingly dense CRFR1 binding in the shell of the NAcc in the montane vole. Montane vole (H) and pine vole (I) brain sections showing the species difference in CRFR1 binding in the laterodorsal thalamus. Montane vole (K) and pine vole (L) hindbrain section highlighting the superior colliculus. Acetylcholinesterase-stained adjacent sections are shown to the left of each panel. Scale bar = 1 mm in C (applies to A,B,C), L (applies to D–L).
Fig. 5
Fig. 5
CRFR2 binding in promiscuous montane and monogamous pine vole species. Montane vole (B) and pine vole (C) sections through the striatum. Note that the species difference in CRFR2 in the septal pole of the NAcc is in the same direction as the meadow versus prairie comparison. Montane vole (E) and pine vole (F) brain sections through the lateral septum. Note that the species difference in CRFR2 in the lateral septum is in the opposite direction as the meadow versus prairie comparison. Montane vole (H) and pine vole (I) brain sections through the hippocampus. Note the species differences in the CA1 fields and the laterodorsal thalamus. Montane vole (K) and pine vole (L) hindbrain sections through the dorsal raphe nucleus. Acetylcholinesterase-stained adjacent sections are shown to the left of each panel. Scale bar = 1 mm in L (applies to A–L).
Fig. 6
Fig. 6
Sex differences in CRFR2 binding in the BnST in promiscuous meadow and monogamous prairie voles. A: Rat brain schematic of the medial caudal, or encapsulated, BnST and fornix (Paxinos and Watson, 1998). B: Meadow male. C: Prairie male. D: Acetylcholinesterase staining of an adjacent brain section through the BnST. E: Meadow female. F: Prairie female. Note the CRFR2 binding in the choroid plexus (ChP) is roughly equivalent across sex and species. Scale bar = 1 mm in F (applies to A–F).
Fig. 7
Fig. 7
Sex differences in CRFR2 binding in the BnST in promiscuous montane and monogamous pine voles. A: Rat brain schematic of the medial caudal, or encapsulated, BnST and fornix (Paxinos and Watson, 1998). (B) Montane male. (C) Pine male. (D) Acetylcholinesterase staining of an adjacent brain section through the BnST. (E) Montane female. (F) Pine female. Note the CRFR2 binding in the choroid plexus (ChP) is roughly equivalent across sex and species. Scale bar = 1 mm in F (applies to A–F).

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