A double‐hit model reveals individual and synergic consequences of prenatal and adolescent postnatal ethanol exposure

PAUTASSI, RICARDO MARCOS; FABIO, MARÍA CAROLINA

ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH

WILEY-BLACKWELL PUBLISHING, INC

Año: 2022

0145-6008

Prenatal alcohol exposure is highly prevalent worldwide. In Argentina, Lichtenberger et al. (2020) reported that 2 out of 10 women reported drinking during pregnancy. Reports from the US, in turn, suggest that around 5% of pregnant women endorse binge drinking (i.e., the ingestion of four standard drinks in a single and usually brief drinking episode) sometime at pregnancy (Popovaet al., 2017). Prenatal EtOH exposure (PEE) is associated with a myriad of consequences, namely neuroanatomical alterations that translate into neuropsychological deficits and mental disorders,including attentional deficits and greater likelihood of being diagnosed with autism spectrum disorder, mental retardation (Geier & Geier, 2022) or with a group of conditions known as fetal alcohol spectrum disorders (FASDs) (Palmeter et al., 2021). Other studies suggest that PEE is associated with lingering changes in EtOH sensitivity or acceptance during infancy or adolescence, when voluntary EtOH drinking begins and escalates. Illustrating this, a seminal study indicated that PEE was the best predictor of adolescent involvement with EtOH, over and beyond relevant ariables,such as nicotine exposure or a positive family history of alcohol use disorder (Baer et al., 2003). In our lab, in turn, we have shown that rats with a history of PEE exhibit, when compared to control counterparts, heightened EtOH intake (Fabio et al., 2013) and greater EtOH-induced conditioned place preference (Pautassi et al., 2012), a measure of conditioned reward. These findings highlight that those exposed to EtOH in utero may be more likely to seek EtOH-related cues or engage in heavy EtOH drinking, a hypothesis put forward—with an emphasis in the putative development of classical conditioning involving EtOH´s chemosensory cues—in the seminal review by Spear andMolina (2005). Later, Miller and Spear (2006) pinpointed synergic effects between prenatal, infantile and adolescent exposure to EtOH. The hypothesis, known as the “generator of alcoholism”, suggests that EtOH exposure at any of these developmental periods facilitates the likelihood, and exacerbates the detrimental effects, of the subsequent EtOH exposures. As described, clinicalwork has shown that PEE is associated with heightened EtOH intake at adolescence (Alati et al., 2006; Baer et al., 2003). An early onset of alcohol use, in turn, is a significant risk factor for hazardous alcohol use and for experiencing alcohol-related negative consequences, including injuries, interpersonal violence and academic or work-related problems (Gruber et al., 1996; Vera et al., 2020). Given this background, it is noteworthy the relatively lack of pre-clinical studies assessing the impairments associated with “double hit exposure” protocols, in which subjects that undergo PEE are given postnatal exposure at adolescence. More in detail, there are plenty of studies assessing how PEE affects subsequent responsivity to EtOH, at infancy (Pueta et al., 2011), adolescence or adulthood (Doremus-Fitzwater et al., 2020), yet to our knowledge there is a scarcity of studies assessing synergic effects between PEE and heavy and protracted EtOH exposure at dolescence.