PMID- 24321744 OWN - NLM STAT- MEDLINE DCOM- 20140306 LR - 20161125 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 225 IP - 1 DP - 2014 Feb 10 TI - Prenatal buprenorphine exposure decreases neurogenesis in rats. PG - 92-101 LID - S0378-4274(13)01457-4 [pii] LID - 10.1016/j.toxlet.2013.12.001 [doi] AB - Perinatal opioid exposure has a negative effect on neurogenesis and produces neurological consequences. However, its mechanisms of action are incompletely understood. Buprenorphine, a mixed opioid agonist/antagonist, is an alternative medication for managing pregnant opioid addicts. This study provides evidence of decreased neurogenesis and depression-like consequences following prenatal exposure to buprenorphine and sheds light on mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant rats starting from gestation day 7 and lasting for 14 days and a cultured neurosphere model. Results of forced swimming test and tail suspension test showed that pups at postnatal day 21 had worse parameters of depression-like neurobehaviors, independent of gender. Neurobehavioral changes were accompanied by reduction of neuronal composition, biochemical parameters of neural stem/progenitor cells, brain-derived neurotrophic factor (BDNF) expression, tropomyosin-related kinase receptor type B phosphorylation, protein kinase A (PKA) activity, and cAMP response element-binding protein phosphorylation. Results of parallel cell studies further demonstrated a negative impact of buprenorphine on cultured neurospheres, including proliferation, differentiation, BDNF expression and signaling, and PKA activity. Taken together, our results suggest that prenatal exposure to buprenorphine might result in depression-like phenotypes associated with impaired BDNF action and decreased neurogenesis in the developing brain of weanlings. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Wu, Chih-Cheng AU - Wu CC AD - Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan; Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan. FAU - Hung, Chih-Jen AU - Hung CJ AD - Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan; Graduate School of Nursing, HungKuang University, Taichung 433, Taiwan. FAU - Shen, Ching-Hui AU - Shen CH AD - Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan. FAU - Chen, Wen-Ying AU - Chen WY AD - Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan. FAU - Chang, Cheng-Yi AU - Chang CY AD - Department of Surgery, Feng Yuan Hospital, Taichung 420, Taiwan. FAU - Pan, Hung-Chuan AU - Pan HC AD - Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 407, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan. FAU - Liao, Su-Lan AU - Liao SL AD - Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan. FAU - Chen, Chun-Jung AU - Chen CJ AD - Graduate School of Nursing, HungKuang University, Taichung 433, Taiwan; Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan; Center for General Education, Tunghai University, Taichung 407, Taiwan. Electronic address: cjchen@vghtc.gov.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131207 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Analgesics, Opioid) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 40D3SCR4GZ (Buprenorphine) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - Analgesics, Opioid/administration & dosage/*toxicity MH - Animals MH - Behavior, Animal/drug effects MH - Brain-Derived Neurotrophic Factor/metabolism MH - Buprenorphine/administration & dosage/*toxicity MH - CREB-Binding Protein/metabolism MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - Depression/chemically induced/physiopathology/psychology MH - Dose-Response Relationship, Drug MH - Female MH - Gestational Age MH - Injections, Intraperitoneal MH - Male MH - Maternal Exposure MH - Motor Activity/drug effects MH - Nervous System/*drug effects/growth & development/metabolism/pathology/physiopathology MH - Neurogenesis/*drug effects MH - Neurons/*drug effects/metabolism/pathology MH - Phosphorylation MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/drug effects/metabolism MH - Signal Transduction/drug effects MH - Spheroids, Cellular MH - Swimming MH - Time Factors OTO - NOTNLM OT - Depression OT - Neurogenesis OT - Neurotrophin OT - Opioid EDAT- 2013/12/11 06:00 MHDA- 2014/03/07 06:00 CRDT- 2013/12/11 06:00 PHST- 2013/09/12 00:00 [received] PHST- 2013/11/05 00:00 [revised] PHST- 2013/12/02 00:00 [accepted] PHST- 2013/12/11 06:00 [entrez] PHST- 2013/12/11 06:00 [pubmed] PHST- 2014/03/07 06:00 [medline] AID - S0378-4274(13)01457-4 [pii] AID - 10.1016/j.toxlet.2013.12.001 [doi] PST - ppublish SO - Toxicol Lett. 2014 Feb 10;225(1):92-101. doi: 10.1016/j.toxlet.2013.12.001. Epub 2013 Dec 7.