Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring

Mauro Ceccanti, Roberto Coccurello, Valentina Carito, Stefania Ciafrè, Giampiero Ferraguti, Giacomo Giacovazzo, Rosanna Mancinelli, Paola Tirassa, George N. Chaldakov, Esterina Pascale, Marco Ceccanti, Claudia Codazzo, Marco Fiore

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Abstract

Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75NTR, TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75NTR in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

Original languageEnglish
Pages (from-to)776-787
Number of pages12
JournalAddiction Biology
Volume21
Issue number4
DOIs
Publication statusPublished - Jul 1 2016

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Keywords

  • Ethanol intake preference
  • neurotrophin
  • paternal alcohol exposure

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Pharmacology

Cite this

Ceccanti, M., Coccurello, R., Carito, V., Ciafrè, S., Ferraguti, G., Giacovazzo, G., Mancinelli, R., Tirassa, P., Chaldakov, G. N., Pascale, E., Ceccanti, M., Codazzo, C., & Fiore, M. (2016). Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring. Addiction Biology, 21(4), 776-787. https://doi.org/10.1111/adb.12255