ETHANOL-RELATED LEARNING IN RAT NEONATES IMPACT UPON APNEIC EPISODES AND PROMOTE SEEKING BEHAVIOR OF STIMULI THAT SIGNALED THE STATE OF INTOXICATION

MARIA BELEN ACEVEDO ; ANUNZIATA FLORENCIA; D'ALOISIO GENESIS; JUAN CARLOS MOLINA

Conferencia; IX INTERNATIONAL MEETING OF THE LATIN AMERICAN SOCIETY FOR BIOMEDICAL RESEARCH ON ALCOHOLISM (LASBRA) NOVEMBER 7TH, 8TH AND 9TH, 2019. ?DETERMINANTS OF ALCOHOLISM: BRIDGING THE GAP BETWEEN EPIDEMIOLOGICAL AND BASIC RESEARCH?; 2019

In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development thatimpact on social and cognitive abilities. This stage in development partially overlaps with the 3rd humangestational trimester in terms of synaptogenesis. At this stage, human fetuses and rat neonates (postnataldays, PDs 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism given explicit associationsbetween exteroceptive stimuli and the state of EtOH intoxication. The present study was meant to analyzehow apneic episodes are affected by the drug itself or through learning processes involving this psychotropic agent. During PDs 3, 5, 7 and 9 rats were subjected to differential experiences with salient tactile cuesexplicitly paired or not with the effects of vehicle or EtOH (2.0 g/kg) intragastric administration. A tactilediscrimination paradigm applied during PDs 3, 5, 7 and 9 was conducted under stressful circumstances(maternal deprivation, exposure to a novel environment and drug administration procedure) for the developing organism. Pups were individually tested in a whole body plethysmograph where a given tactile cue waspresented under the state of sobriety while an alternative texture was associated with the state of intoxication. Ethanol intoxication systematically inhibited the occurrence of apneic episodes. Most importantly, itwas observed that tactile cues (either smooth or rough) systematically paired with ethanol intoxication alsopromoted inhibitory effects upon the emergence of apneas (isodirectional conditioned response). The studyalso revealed that ethanol also results in a sensitization process relative to its inhibitory effects upon apneicepisodes. At PD11, pups were tested in a two-way tactile preference test defined by the textures previouslyexperienced. This test revealed that ethanol intoxication increased preferences towards the stimuli that predicted such a toxic state. These last results may imply both the systematically reported positive reinforcingeffects of ethanol during early ontogeny and/or its negative reinforcement capability in terms of antianxietyeffects. As a whole these results emphasize the need to consider ethanol?s motivational effects during earlydevelopment upon the regulation of breathing patterns and subsequent affinity for the drug.