Chela M Wallin1, Scott E Bowen2, Chelsea L Roberge3, Lauren M Richardson4, Susanne Brummelte5. 1. Department of Psychology, Wayne State University, Detroit, MI, 48202, USA. Electronic address: Chela.Wallin@wayne.edu. 2. Department of Psychology, Wayne State University, Detroit, MI, 48202, USA. Electronic address: scottbowen@wayne.edu. 3. Department of Psychology, Wayne State University, Detroit, MI, 48202, USA. Electronic address: el8769@wayne.edu. 4. Department of Psychology, Wayne State University, Detroit, MI, 48202, USA. Electronic address: gh1837@wayne.edu. 5. Department of Psychology, Wayne State University, Detroit, MI, 48202, USA. Electronic address: sbrummelte@wayne.edu.
Abstract
BACKGROUND: The opioid crisis has led to an increased number of pregnant opioid-dependent women receiving opioid-maintenance therapy (e.g. buprenorphine, BUP), but little is known about the consequences of gestational BUP exposure on pregnancy outcomes, maternal care, or offspring development. METHODS: Our translational rodent model began BUP exposure to adult female rats (N = 30) at least 7 days before conception and continued throughout the postpartum period. Both therapeutic low-dose (BUP-LD, 0.3 mg/kg, s.c.) and overexposure high-dose (BUP-HD, 1.0 mg/kg) doses of BUP were compared to saline control. Female rats were bred in house with drug-naïve adult male rats. The day after parturition, litters were culled to 5 males/5 females and assigned randomly to various behavioral tests and assessed either neonates or adolescents. Litter characteristics, maternal caregiving, Neonatal Opioid Withdrawal Syndrome (NOWS), offspring development and adolescent behaviors were evaluated. RESULTS: BUP-LD decreased maternal care, delayed offspring development, decreased offspring body weight, length, temperature, and pain sensitivity (p's < .05). BUP-HD drastically reduced maternal care and offspring survival, altered litter characteristics, and increased NOWS (p's < .05). CONCLUSION: These results demonstrate that the therapeutic BUP-LD in rats was relatively safe with subtle effects on maternal care and rodent offspring. However, overexposure BUP-HD in rats produced NOWS and compromised maternal caregiving as well as rodent offspring survival. More research is critical to validate the translational implication of these findings for human opioid-dependent mothers maintained on BUP-maintenance therapy.
BACKGROUND: The opioid crisis has led to an increased number of pregnant opioid-dependent women receiving opioid-maintenance therapy (e.g. buprenorphine, BUP), but little is known about the consequences of gestational BUP exposure on pregnancy outcomes, maternal care, or offspring development. METHODS: Our translational rodent model began BUP exposure to adult female rats (N = 30) at least 7 days before conception and continued throughout the postpartum period. Both therapeutic low-dose (BUP-LD, 0.3 mg/kg, s.c.) and overexposure high-dose (BUP-HD, 1.0 mg/kg) doses of BUP were compared to saline control. Female rats were bred in house with drug-naïve adult male rats. The day after parturition, litters were culled to 5 males/5 females and assigned randomly to various behavioral tests and assessed either neonates or adolescents. Litter characteristics, maternal caregiving, Neonatal Opioid Withdrawal Syndrome (NOWS), offspring development and adolescent behaviors were evaluated. RESULTS:BUP-LD decreased maternal care, delayed offspring development, decreased offspring body weight, length, temperature, and pain sensitivity (p's < .05). BUP-HD drastically reduced maternal care and offspring survival, altered litter characteristics, and increased NOWS (p's < .05). CONCLUSION: These results demonstrate that the therapeutic BUP-LD in rats was relatively safe with subtle effects on maternal care and rodent offspring. However, overexposure BUP-HD in rats produced NOWS and compromised maternal caregiving as well as rodent offspring survival. More research is critical to validate the translational implication of these findings for human opioid-dependent mothers maintained on BUP-maintenance therapy.
Authors: Caitlin R Schlagal; Tiffany J Dunn; Pei Xu; Daniel E Felsing; Christina R Merritt; Sanjana Manja; Robert G Fox; Shelly A Buffington; George Saade; Kelly T Dineley; Yongjia Yu; Kathryn A Cunningham; Ping Wu Journal: Neuroscience Date: 2021-03-31 Impact factor: 3.708
Authors: Gregory G Grecco; Briana E Mork; Jui-Yen Huang; Corinne E Metzger; David L Haggerty; Kaitlin C Reeves; Yong Gao; Hunter Hoffman; Simon N Katner; Andrea R Masters; Cameron W Morris; Erin A Newell; Eric A Engleman; Anthony J Baucum; Jiuen Kim; Bryan K Yamamoto; Matthew R Allen; Yu-Chien Wu; Hui-Chen Lu; Patrick L Sheets; Brady K Atwood Journal: Elife Date: 2021-03-16 Impact factor: 8.140