Early life stress as a risk factor for substance use disorders: Clinical and neurobiological substrates

Sajoy Varghese*, Janitza Montalvo-Ortiz, John Csernansky, Rodney Eiger, Amy Herrold, Maju Koola, Hongxin Dong

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Early Life Stress (ELS) can profoundly influence an individual′s genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Materials and Methods: Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA) was used for this study. Morphine (10 mg/kg) was administered every other day for 10 days or with increasing doses of morphine: 20, 40, 60, 80, 100, and 100 mg/kg. The behavioral trials including morphine sensitization, Somatic Opiate Withdrawal Symptoms (SOWS) were conducted in a single, open field, activity. After behavioral trial, animals were perfused for immunohistochemistry analysis. Results: CRF-over expressed (CRF-OE) mice showed increase in morphine sensitization and withdrawal symptoms after morphine administration compared to wild type (WT) mice. The two-way ANOVA in the morphine sensitization study showed a significant effect of treatment (P<0.05) and genotype for distance traveled (P<0.01). In the SOWS study, opiate withdrawal symptoms such as rearings, circling behavior, grooming, and jump in CRF-OE were amplified in parallel to WT mice. In the immunohistochemistry study, pro-dynorphine (PDYN) expression was increased after morphine administration in both amygdala and nucleus accumbens (NAcc). Conclusions: CRF-OE in the forebrain increases the sensitization and withdrawal symptoms in morphine treated mice. On exposure to morphine, in CRF-OE mice the PDYN protein expression was increased as compared to WT mice in the amygdala and NAcc.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalIndian Journal of Psychological Medicine
Issue number1
StatePublished - Jan 1 2015


  • Corticotrophin-releasing factor
  • early life stress
  • morphine
  • opioid use disorder
  • substance use disorders

ASJC Scopus subject areas

  • Clinical Psychology


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