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 ΔFosB 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.

Rapamycin Improves Spatial Learning Deficits, Vulnerability to Alcohol Addiction and Altered Expression of the GluN2B Subunit of the NMDA Receptor in Adult Rats Exposed to Ethanol during the Neonatal Period

“…It should be noted that such effects were observed at the ethanol doses that did not induce significant changes in the animal's locomotor activity. Thus, our results are in agreement with previous work demonstrating that prenatal ethanol exposure increases alcohol preference in later life in humans [11] and in rodents [61,62] and confirm that the drug's rewarding properties not associated with the sensitivity to its locomotor stimulation effect [12,63,64]. In our study, rapamycin, the mTORC1 inhibitor, given before ethanol administration during the neonatal period prevented the sensitivity to rewarding effects of ethanol in adulthood.…”

Effects of High-Fat Diet and Maternal Binge-Like Alcohol Consumption and Their Influence on Cocaine Response in Female Mice Offspring

“…Pregnant and nursing C57BL/6 mice were exposed to alcohol following the DID paradigm ( Rhodes et al, 2005 ). The procedure was conducted as previously reported ( Cantacorps et al, 2017 , 2020 ) starting 2 days after mating. Pregnant female mice were randomly assigned to 2 groups: alcohol and water exposed (control).…”

“…In this sense, Barbier et al (2008) reported that alcohol-exposed male offspring are more sensitive to the anxiolytic effect of ethanol, a feature that could partially explain the altered pattern of consumption of alcohol observed in these animals. Furthermore, it has been described that maternal binge-like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine and thus enhances vulnerability to cocaine addiction in adult mice ( Cantacorps et al, 2020 ).…”

The Transgenerational Consequences of the Interaction Between Humans and Molecules: Alcohol as a Cultural Artifact

“…Considering the role of the dopaminergic system in the genesis of drug addiction, this finding can provide a mechanistic explanation for the increased risk of drug dependence in individuals who experienced an early exposure to ethanol (Figure 1). Other structures known to be involved in addictive behavior, such as the medial prefrontal cortex and the amygdala, are also affected by early exposure to alcohol and might contribute to generate drug dependence during later life (Baculis et al, 2015;Sharp, 2017;Cantacorps et al, 2019). Permanent consequences of early contacts with alcohol can be also explained by epigenetic mechanisms, i.e., by the long-lasting chemical modifications of DNA, some of which are known to be induced by ethanol (e.g., Mead and Sarkar, 2014;Cobben et al, 2019).…”