TY - JOUR
T1 - Differential sensitivity of alcohol drinking and partner preference to a CRFR1 antagonist in prairie voles and mice
AU - Potretzke, Sheena
AU - Robins, Meridith T.
AU - Ryabinin, Andrey E.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - Available pharmacotherapies to treat alcohol use disorder (AUD) show limited efficacy. Preclinical studies in mice and rats suggested that antagonists of the corticotropin releasing factor receptor 1 (CRFR1) could be more efficacious for such treatment. However, clinical trials with CRFR1 antagonists were not successful. While a number of potential explanations for this translational failure have been suggested, we hypothesized that the lack of success in clinical trials could be in part due to different neuroanatomical organization of the CRFR1 system in mice and rats versus humans. The CRF system in prairie voles (Microtus ochrogaster), a socially monogamous rodent species, also shows differences in organization from mice and rats. To test our hypothesis, we compared the efficacy of a potent CRFR1 antagonist, CP-376,395, to modulate alcohol drinking in male and female prairie voles versus male and female C57BL/6J mice using an almost identical 2-bottle choice drinking procedure. CP-376,375 (10 and 20 mg/kg, i.p.) significantly decreased alcohol intake (but not alcohol preference) in mice, but not prairie voles. Furthermore, administration of this antagonist (20 mg/kg, i.p.) prior to the partner preference test (PPT) decreased partner preference (PP) in male prairie voles. These findings support our hypothesis that the greater efficacy of CRFR1 antagonists to suppress alcohol consumption in mice and rats versus other mammalian species could be due to the differences in organization of the CRFR1 system between species. They further indicate that activity of the CRFR1 system is necessary for the formation of pair-bonds, but not consumption of high doses of alcohol. Overall, we suggest that testing potential pharmacotherapies should not rely only on studies in mice and rats.
AB - Available pharmacotherapies to treat alcohol use disorder (AUD) show limited efficacy. Preclinical studies in mice and rats suggested that antagonists of the corticotropin releasing factor receptor 1 (CRFR1) could be more efficacious for such treatment. However, clinical trials with CRFR1 antagonists were not successful. While a number of potential explanations for this translational failure have been suggested, we hypothesized that the lack of success in clinical trials could be in part due to different neuroanatomical organization of the CRFR1 system in mice and rats versus humans. The CRF system in prairie voles (Microtus ochrogaster), a socially monogamous rodent species, also shows differences in organization from mice and rats. To test our hypothesis, we compared the efficacy of a potent CRFR1 antagonist, CP-376,395, to modulate alcohol drinking in male and female prairie voles versus male and female C57BL/6J mice using an almost identical 2-bottle choice drinking procedure. CP-376,375 (10 and 20 mg/kg, i.p.) significantly decreased alcohol intake (but not alcohol preference) in mice, but not prairie voles. Furthermore, administration of this antagonist (20 mg/kg, i.p.) prior to the partner preference test (PPT) decreased partner preference (PP) in male prairie voles. These findings support our hypothesis that the greater efficacy of CRFR1 antagonists to suppress alcohol consumption in mice and rats versus other mammalian species could be due to the differences in organization of the CRFR1 system between species. They further indicate that activity of the CRFR1 system is necessary for the formation of pair-bonds, but not consumption of high doses of alcohol. Overall, we suggest that testing potential pharmacotherapies should not rely only on studies in mice and rats.
KW - Affiliation
KW - Alcohol
KW - Animal models
KW - CRH receptor 1
KW - Corticotropin-releasing hormone
KW - Partner preference
KW - Prairie vole
UR - http://www.scopus.com/inward/record.url?scp=85077922226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077922226&partnerID=8YFLogxK
U2 - 10.1016/j.yhbeh.2020.104676
DO - 10.1016/j.yhbeh.2020.104676
M3 - Article
C2 - 31927017
AN - SCOPUS:85077922226
SN - 0018-506X
VL - 120
JO - Hormones and Behavior
JF - Hormones and Behavior
M1 - 104676
ER -