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Toxicol Lett. 2014 Feb 10;225(1):92-101. doi: 10.1016/j.toxlet.2013.12.001. Epub 2013 Dec 7.

Prenatal buprenorphine exposure decreases neurogenesis in rats.

Author information

1
Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan; Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan.
2
Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan; Graduate School of Nursing, HungKuang University, Taichung 433, Taiwan.
3
Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan.
4
Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
5
Department of Surgery, Feng Yuan Hospital, Taichung 420, Taiwan.
6
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung 407, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
7
Department of Education and Research, Taichung Veterans General Hospital, Taichung 407, Taiwan.
8
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.

Abstract

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.

KEYWORDS:

Depression; Neurogenesis; Neurotrophin; Opioid

PMID:
24321744
DOI:
10.1016/j.toxlet.2013.12.001
[Indexed for MEDLINE]

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