title: Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
authors: Emilia
authors: E
authors: Romano
authors: Federica
authors: F
authors: De Angelis
authors: Lisa
authors: L
authors: Ulbrich
authors: Antonella
authors: A
authors: De Jaco
authors: Andrea
authors: A
authors: Fuso
authors: Giovanni
authors: G
authors: Laviola
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006579:Heterozygote; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D000091042:Reelin Protein; D009538:Nicotine; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1