Development of anxiety-like behavior via hippocampal IGF-2 signaling in the offspring of parental morphine exposure: Effect of enriched environment

Chang Qi Li, Yan Wei Luo, Fang Fang Bi, Tao Tao Cui, Ling Song, Wen Yu Cao, Jian Yi Zhang, Fang Li, Jun Mei Xu, Wei Hao, Xiao Wei Xing, Fiona H. Zhou, Xin Fu Zhou, Ru Ping Dai

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44 Citations (Scopus)


Opioid addiction is a major social, economic, and medical problem worldwide. Long-term adverse consequences of chronic opiate exposure not only involve the individuals themselves but also their offspring. Adolescent maternal morphine exposure results in behavior and morphologic changes in the brain of their adult offspring. However, few studies investigate the effect of adult opiate exposure on their offspring. Furthermore, the underlying molecular signals regulating the intergenerational effects of morphine exposure are still elusive. We report here that morphine exposure of adult male and female rats resulted in anxiety-like behavior and dendritic retraction in the dentate gyrus (DG) region of the hippocampus in their adult offspring. The behavior and morphologic changes were concomitant with the downregulation of insulin-like growth factor (IGF)-2 signaling in the granular zone of DG. Overexpression of hippocampal IGF-2 by bilateral intra-DG injection of lentivirus encoding the IGF-2 gene prevented anxiety-like behaviors in the offspring. Furthermore, exposure to an enriched environment during adolescence corrected the reduction of hippocampal IGF-2 expression, normalized anxiety-like behavior and reversed dendritic retraction in the adult offspring. Thus, parental morphine exposure can lead to the downregulation of hippocampal IGF-2, which contributed to the anxiety and hippocampal dendritic retraction in their offspring. An adolescent-enriched environment experience prevented the behavior and morphologic changes in their offspring through hippocampal IGF-2 signaling. IGF-2 and an enriched environment may be a potential intervention to prevention of anxiety and brain atrophy in the offspring of parental opioid exposure.

Original languageEnglish
Pages (from-to)2777-2787
Number of pages11
Issue number12
Publication statusPublished or Issued - Nov 2014

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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