Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Abstract

BACKGROUND AND PURPOSE: Alcohol exposure in utero may lead to a wide range of long-lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long-term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward-related behaviours in adult offspring. EXPERIMENTAL APPROACH: Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking-in-the-dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine-induced motivational responses (conditioned place preference, behavioural sensitization and operant self-administration). Protein expression of dopamine- and glutamate-related molecules was assessed following cocaine-induced reinstatement. KEY RESULTS: The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine-paired chamber in the conditioned place preference test. Furthermore, early alcohol-exposed mice displayed attenuated cocaine-induced behavioural sensitization but also higher cocaine self-administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ¿FosB expression were found in the prefrontal cortex and the striatum of alcohol-exposed mice after cocaine-primed reinstatement. CONCLUSION AND IMPLICATIONS: Our findings demonstrate that maternal binge-like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol-exposed offspring to develop drug addiction later in adulthood.

This study was supported by the European Union's Horizon 2020 research and innovation program 2014-2020 under Grant Agreement 634143, Ministerio de Economía y Competitividad (SAF2016-75347-R), and Ministerio de Sanidad of the Spanish government (Retic-ISCIII-RD/16/0017/0010-FEDER and Plan Nacional sobre Drogas 2018/007). L.C. received a FPI grant from the Ministerio de Economía y Competitividad (BES-2014-070657), M.A.L. received an FPU fellowship from the Ministerio de Educación, Cultura y Deporte (15/02492), and S.M.R. received an APOSTD/2017/102 European Social fund grant from the Generalitat Valenciana. The Department of Experimental and Health Sciences (UPF) is an "Unidad de Excelencia María de Maeztu" funded by the MINECO (Ref. MDM-2014-0370). The authors thank Gerald-Patrick Fannon for his English proof reading and editing of the manuscript.