Fetal ethanol exposure increases ethanol intake by making it smell and taste better

Abstract

Human epidemiologic studies reveal that fetal ethanol exposure is highly predictive of adolescent ethanol avidity and abuse. Little is known about how fetal exposure produces these effects. It is hypothesized that fetal ethanol exposure results in stimulusinduced chemosensory plasticity. Here, we asked whether gestational ethanol exposure increases postnatal ethanol avidity in rats by altering its taste and odor. Experimental rats were exposed to ethanol in utero via the dam's diet, whereas control rats were either pair-fed an iso-caloric diet or given food ad libitum. We found that fetal ethanol exposure increased the taste-mediated acceptability of both ethanol and quinine hydrochloride (bitter), but not sucrose (sweet). Importantly, a significant proportion of the increased ethanol acceptability could be attributed directly to the attenuated aversion to ethanol's quinine-like taste quality. Fetal ethanol exposure also enhanced ethanol intake and the behavioral response to ethanol odor. Notably, the elevated intake of ethanol was also causally linked to the enhanced odor response. Our results demonstrate that fetal exposure specifically increases ethanol avidity by, in part, making it taste and smell better. More generally, they establish an epigenetic chemosensory mechanism by which maternal patterns of drug use can be transferred to offspring. Given that many licit (e.g., tobacco products) and illicit (e.g., marijuana) drugs have noteworthy chemosensory components, our findings have broad implications for the relationship between maternal patterns of drug use, child development, and postnatal vulnerability. chemosensory plasticity ͉ ethanol acceptability ͉ olfaction ͉ bitter ͉ gustation F etal ethanol exposure can have significant negative consequences for the developing human fetus. Fetal alcohol spectrum disorder describes a continuum of sequelae that can range from craniofacial malformations and mental retardation to behavioral changes such as hyperactivity and learning and memory deficits (1). There are also subtler, but nevertheless significant, clinical effects of fetal ethanol exposure. For instance, human epidemiologic studies (2, 3) report that (i) fetal ethanol exposure increases the risk of adolescent ethanol abuse, (ii) gestational exposure is the best predictor of adolescent abuse, and (iii) the earlier the age of secondary postnatal ethanol exposure, the greater the chance of long-term alcoholism. Little is known about how fetal exposure produces these changes in ethanol avidity.Numerous studies have examined how ethanol consumption during pregnancy alters the perception, preference, and consumption of ethanol by the mother's offspring. Animal studies (4, 5) have established that (i) ingested alcohol diffuses into amniotic fluid, (ii) fetuses ingest amniotic fluid and sense intrauterine ethanol, and (iii) the fetus can acquire information about ethanol-related sensory cues and display a memory of this prenatal experience. Likewise, human studies indicate that the fetus can detect and remember p...

The effect of taste familiarity on intake and taste reactivity in infant rats

“…However, since in that study the familiarization procedure involved the ingestion of relatively large amounts of ethanol, sufficient to induce pharmacological effects, it may be concluded that the reported effect was the consequence of an appetitive association between ethanol's flavor and its reinforcing properties, rather than solely an effect of familiarization. Likewise, when comparing the present results with those of studies involving prenatal ethanol exposure in which increased intake, enhanced palatability and even odor preference were observed (Abate et al, 2008;Chotro et al, 2007Chotro et al, , 2009Spear & Molina, 2005;Youngentob & Glendinning, 2009), it remains clear that in all those studies the experience with ethanol necessarily involved a reinforcer in addition to ethanol's flavor.…”

“…In another study with rat fetuses, no differential responsiveness to a mint flavor was found after analyzing eleven behavioral categories of the fetal response as a function of familiarity (Smotherman & Robinson, 1985). With the flavor of ethanol, which is a complex stimulus with gustatory, olfactory and irritant components, it has been found that prenatal exposure induces increased intake and/or enhanced palatability of ethanol in infant and older rats (Abate, Pueta, Spear, & Molina, 2008;Chotro, Arias, & Laviola, 2007;Youngentob & Glendinning, 2009) (Chotro, Arias, & Spear, 2009). Although in most of this research exposure to ethanol also involved the presence of reinforcing consequences, it should be pointed out that when the contiguity of ethanol's flavor with reinforcement was explicitly avoided, no changes were observed either in ethanol consumption (Arias & Chotro, 2006;Chotro & Alonso, 2003;Chotro & Arias, 2003;Chotro et al, 2009) or in reactivity to its flavor (Arias & Chotro, 2005;Dominguez, Chotro, & Molina, 1993;Molina & Chotro, 1991).…”

Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors

“…Extensive basic research in animal models demonstrates that prenatal or early neonatal alcohol exposure alters a variety of later behavioral (Abate, et al, 2008; Becker et al, 1993; 1993; Chotro & Arias, 2006; Middleton et al, 2009; March et al, 2009), consummatory (Chotro et al, 2007; Diáz-Cenzano et al, 2014; Miranda-Morales et al, 2014; Shea et al, 2012; Youngentob & Glendinning. 2009), pharmacological (Diáz-Cenzano et al, 2014; Pautassi et al, 2012), biochemical (Middleton et al, 2009), and physiological (Eade et al, 2010; Taylor et al, 1981; Weinberg et al, 1995) responses to alcohol.…”

“…2009), pharmacological (Diáz-Cenzano et al, 2014; Pautassi et al, 2012), biochemical (Middleton et al, 2009), and physiological (Eade et al, 2010; Taylor et al, 1981; Weinberg et al, 1995) responses to alcohol. Possible means by which PAE influences postnatal responses to and ingestion of alcohol include altered chemosensory experiences of alcohol and/or learning about the rewarding (or aversive) properties of alcohol cues in utero (e.g., Arias & Chotro, 2005; Chotro & Arias, 2006; Chotro et al, 1991; 2009; March et al, 2009; Pautassi et al, 2012; Youngentob & Glendinning, 2009); ideas articulated well in the theoretical review by N. Spear and Molina (2005).…”

“…Spear & Molina, 2005), including altered learned responses to paired alcohol odors and tastes after brief PAE (Abate et al, 2000; Arias & Chotro, 2005; Chotro, et al, 1991; Pautassi et al, 2012). In rats, even low-dose alcohol exposure during fetal development is associated with later increases in alcohol ingestion (Abate et al, 2008; Chotro & Arias, 2006; Chotro & Molina, 1990; Youngentob & Glendinning, 2009). …”