, Volume 231, Issue 8, pp 1775–1787 | Cite as

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
Original Investigation



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.


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.


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.


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.


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.


Adolescence Nicotine Tobacco Behavioral disorders Cognition Animal models Reelin 



Glutamic acid decarboxylase


Heterozygous reeler mice


Brain-derived neurotrophic factor


Acetylcholine nicotinic receptors


DNA methyltransferase 1



We are grateful to Giovanni Dominici for animal care. E.R. is supported by a fellowship from the ERAnet "PrioMedChild", Italian Ministry of Health (P.I. Walter Adriani). The authors are grateful to Dr. Saira Shamsi for critical reading of the manuscript. This research was supported by IRE-IFO (RF2008) "MECP2 phosphorilation and related kinase in Rett syndrome" to GL, E.R. is recipient of a Postdoctoral fellowship under the "NeuroGenMRI" project in the framework of ERAnet "PrioMedChild" Program.

Conflict of interest

We also declare no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Emilia Romano
    • 1
    • 2
  • Federica De Angelis
    • 3
  • Lisa Ulbrich
    • 3
  • Antonella De Jaco
    • 3
  • Andrea Fuso
    • 4
  • Giovanni Laviola
    • 1
  1. 1.Section of Behavioural Neuroscience, Department of Cell Biology and NeuroscienceIstituto Superiore di SanitàRomeItaly
  2. 2.Bambino Gesù Children’s Hospital IRCCSRomeItaly
  3. 3.Department of Biology and Biotechnology Charles DarwinSapienza University of RomeRomeItaly
  4. 4.Department of Psychology, Section of NeuroscienceSapienza University of RomeRomeItaly

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