PMID- 24337025 OWN - NLM STAT- MEDLINE DCOM- 20150126 LR - 20211203 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 231 IP - 8 DP - 2014 Apr TI - Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice. PG - 1775-87 LID - 10.1007/s00213-013-3388-y [doi] AB - 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 (alpha7, beta2 and alpha4) 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. FAU - Romano, Emilia AU - Romano E AD - Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161, Rome, Italy. FAU - De Angelis, Federica AU - De Angelis F FAU - Ulbrich, Lisa AU - Ulbrich L FAU - De Jaco, Antonella AU - De Jaco A FAU - Fuso, Andrea AU - Fuso A FAU - Laviola, Giovanni AU - Laviola G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131213 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cell Adhesion Molecules, Neuronal) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nicotinic Agonists) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Nicotinic) RN - 0 (Reelin Protein) RN - 6M3C89ZY6R (Nicotine) RN - EC 3.4.21.- (Reln protein, mouse) RN - EC 3.4.21.- (Serine Endopeptidases) RN - EC 4.1.1.15 (Glutamate Decarboxylase) RN - EC 4.1.1.15 (glutamate decarboxylase 1) SB - IM MH - Administration, Oral MH - Animals MH - Brain/*drug effects/*growth & development/physiology MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Adhesion Molecules, Neuronal/metabolism MH - Cognition/*drug effects/physiology MH - Exploratory Behavior/drug effects/physiology MH - Extracellular Matrix Proteins/metabolism MH - Gene Expression/*drug effects MH - Glutamate Decarboxylase/metabolism MH - Heterozygote MH - Male MH - Maze Learning/drug effects/physiology MH - Mice, Neurologic Mutants MH - Nerve Tissue Proteins/metabolism MH - Nicotine/*pharmacology MH - Nicotinic Agonists/*pharmacology MH - RNA, Messenger/metabolism MH - Receptors, Nicotinic/metabolism MH - Reelin Protein MH - Serine Endopeptidases/metabolism EDAT- 2013/12/18 06:00 MHDA- 2015/01/27 06:00 CRDT- 2013/12/17 06:00 PHST- 2013/06/28 00:00 [received] PHST- 2013/11/30 00:00 [accepted] PHST- 2013/12/17 06:00 [entrez] PHST- 2013/12/18 06:00 [pubmed] PHST- 2015/01/27 06:00 [medline] AID - 10.1007/s00213-013-3388-y [doi] PST - ppublish SO - Psychopharmacology (Berl). 2014 Apr;231(8):1775-87. doi: 10.1007/s00213-013-3388-y. Epub 2013 Dec 13.