Nicotine exposure during adolescence: Cognitive performance and brain gene expression in adult heterozygous reeler mice

Emilia Romano, Federica De Angelis, Lisa Ulbrich, Antonella De Jaco, Andrea Fuso, Giovanni Laviola

Research output: Contribution to journalArticlepeer-review


Rationale: We have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders. Objectives: We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males. Methods: Adolescent mice (pnd 37-42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found. Results: Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (α7, β2 and α4) did not differ between genotypes and as a result of previous nicotine exposure. Conclusion: These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation.

Original languageEnglish
Pages (from-to)1775-1787
Number of pages13
Issue number8
Publication statusPublished - 2014


  • Adolescence
  • Animal models
  • Behavioral disorders
  • Cognition
  • Nicotine
  • Reelin
  • Tobacco

ASJC Scopus subject areas

  • Pharmacology
  • Medicine(all)


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