Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.
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 (p75(NTR) , 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 p75(NTR) 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.
Centro Riferimento Alcologico Regione Lazio, Sapienza University of Rome, Italy.
Mauro
M
Ceccanti
Institute of Cell Biology and Neurobiology (IBCN)/IRCCS S. Lucia Foundation, Italy.
Roberto
R
Coccurello
Institute of Cell Biology and Neurobiology (IBCN)/IRCCS S. Lucia Foundation, Italy.
Valentina
V
Carito
Institute of Translational Pharmacology (IFT), National Research Council of Italy (C.N.R.), Italy.
Stefania
S
Ciafrè
Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
Giampiero
G
Ferraguti
Institute of Cell Biology and Neurobiology (IBCN)/IRCCS S. Lucia Foundation, Italy.
Giacomo
G
Giacovazzo
Centro Nazionale Sostanze Chimiche, Instituto Superiore di Sanità, Rome, Italy.
Rosanna
R
Mancinelli
Institute of Cell Biology and Neurobiology (IBCN)/IRCCS S. Lucia Foundation, Italy.
Paola
P
Tirassa
Laboratory of Cell Biology, Medical University, Bulgaria.
George N
GN
Chaldakov
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Italy.
Esterina
E
Pascale
Department of Neurology and Psychiatry, Sapienza University of Rome, Italy.
Marco
M
Ceccanti
Centro Riferimento Alcologico Regione Lazio, Sapienza University of Rome, Italy.
Claudia
C
Codazzo
Institute of Cell Biology and Neurobiology (IBCN)/IRCCS S. Lucia Foundation, Italy.
Marco
M
Fiore
D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002849:Chromatography, Gas; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D005220:Fathers; D008297:Male; D051379:Mice; D020932:Nerve Growth Factor / Q000187:drug effects*; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D000431:Ethanol; D013395:Sucrose; D020932:Nerve Growth Factor
Ethanol intake preference; neurotrophin; paternal alcohol exposure