title: Depression-like effect of prenatal buprenorphine exposure in rats.
abstract: Studies indicate that perinatal opioid exposure produces a variety of short- and long-term neurobehavioral consequences. However, the precise modes of action are incompletely understood. Buprenorphine, a mixed agonist/antagonist at the opioid receptors, is currently being used in clinical trials for managing pregnant opioid addicts. This study provides evidence of depression-like consequence following prenatal exposure to supra-therapeutic dose of buprenorphine and sheds light on potential mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant Sprague-Dawley rats starting from gestation day 7 and lasting for 14 days. Results showed that pups at postnatal day 21 but not the dams had worse parameters of depression-like neurobehaviors using a forced swimming test and tail suspension test, independent of gender. Neurobehavioral changes were accompanied by elevation of oxidative stress, reduction of plasma levels of brain-derived neurotrophic factor (BDNF) and serotonin, and attenuation of tropomyosin-related kinase receptor type B (TrkB) phosphorylation, extracellular signal-regulated kinase (ERK) phosphorylation, protein kinase A activity, cAMP response element-binding protein (CREB) phosphorylation, and CREB DNA-binding activity. Since BDNF/serotonin and CREB signaling could orchestrate a positive feedback loop, our findings suggest that the induction of oxidative stress, reduction of BDNF and serotonin expression, and attenuation of CREB signaling induced by prenatal exposure to supra-therapeutic dose of buprenorphine provide evidence of potential mechanism for the development of depression-like neurobehavior.
authors.affiliation: Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC ; Graduate School of Nursing, HungKuang University, Taichung, Taiwan, ROC.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Hung
authors.affiliation: Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC ; Department of Financial and Computational Mathematics, Providence University, Taichung, Taiwan, ROC.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, ROC.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Surgery, Fong Yuan Hospital, Taichung, Taiwan, ROC.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Pharmacology, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Kuan
authors.affiliation: Department of Neurosurgery, Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC ; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Hung-Chuan
authors.initials: HC
authors.lastname: Pan
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
authors.forename: Su-Lan
authors.initials: SL
authors.lastname: Liao
authors.affiliation: Graduate School of Nursing, HungKuang University, Taichung, Taiwan, ROC ; Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC ; Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, ROC ; Center for General Education, Tunghai University, Taichung, Taiwan, ROC.
authors.forename: Chun-Jung
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002047:Buprenorphine / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D017392:Thiobarbituric Acid Reactive Substances; D012701:Serotonin; D002047:Buprenorphine; D002374:Catalase; D005979:Glutathione Peroxidase; D005978:Glutathione