FETAL PROGRAMMING OF HEIGHTENED ETHANOL PREFERENCE AND NEONATAL BREATHING DISRUPTIONS: COMMON DENOMINATORS BASED ON ETHANOL-RELATED LEARNING PROCESSES

MACCHIONE AF; ACEVEDO, MB; CASTELLO, S; D'ALOISIO, G; ANUNZIATA, F; TRUJILLO, V.; MOLINA, JC

San Diego

Congreso; 41st Annual RSA Scientific Meeting; 2018

Beyond the well known teratological effects of ethanol, preclinical studies have systematically demonstrated that moderate ethanol doses recruit sensory and learning capabilities of the near term fetus. When ethanol accumulates in the amniotic fluid, the unborn organism processes its chemosensory cues. Familiarization with ethanol´s sensory attributes results in later recognition and acceptance of the odor and taste of the drug. This memory is modulated by different physiological consequences of the state of intoxication. Relative to this issue, a series of studies have been conducted in rats and humans. Preclinical approaches have dealt with functional learning capabilities of the near term fetus and during neonatal life (stages that in terms of brain synaptogenesis are analogous to the 2nd and 3rd human gestational trimesters; respectively). Brief experiences with moderate ethanol doses (0.5-2.0 g/kg) were sufficient to sensitize the developing organism to ethanol´s reinforcing effects. The studies also demonstrated an early capability of associating ethanol´s sensory cues with the reinforcing effects of the drug. The associative memory enhances subsequent ethanol drinking patterns and exacerbates operant-mediated ethanol seeking behaviors. The motivational effects of ethanol coexist with other physiological consequences of the state of intoxication; particularly with a significant respiratory depression. Sequential exposure to the drug also sensitizes the organism towards its disruptive effects upon respiratory neuroplasticity. In turn, the sensitization process favors associative learning mechanisms that comprise the contingency existing between chemosensory perception of ethanol and its depressant respiratory effects. Two additional studies have been conducted in human neonates delivered by infrequent, moderate or frequent drinkers. We employed the Neonatal Facial Coding System to evaluate facial expressions elicited by ethanol odor or a novel scent (lemon). Babies prenatally exposed to the drug exhibited significantly higher appetitive responses to ethanol odor when compared with babies delivered by infrequent drinkers. In a second study, respiratory, cardiac and oxygen saturation parameters were assessed in babies exposed to ethanol odor or lemon. Ethanol odor was found to significantly depress respiratory frequencies in neonates delivered by frequent drinkers. These studies demonstrate that fetal ethanol exposure recruits analogous non-associative (sensitization) and associative learning processes related with the establishment of ethanol preferences and with physiological disruptions of the respiratory system.