Stimulus control of ethanol´s effects upon early respiration patterns.

CULLERÉ, ME; SPEAR, N.E.; MOLINA, J.C.

San Francisco

Congreso; 35th Annual Scientific Meeting of the Research Society on Alcoholism; 2012

Research Society on Alcoholism

STIMULUS CONTROL OF ETHANOL´S EFFECTS UPON EARLY RESPIRATION PATTERNS Cullere´ , ME, Spear, NE, Molina JC Instituto de Investigacio´n Me´dica Mercedes y Martı´n Ferreyra, Co´rdoba, Argentina Preclinical and human studies systematically indicate fetal depression of respiration rates as a function of maternal ethanol exposure. In a variety of experimental studies it has been observed that rat perinates are capable of associating different conditioned stimuli with unconditioned autonomic and motivational effects of the drug. As indicated by prior research, central nervous system maturation patterns of infant rats [postnatal days (PDs) 3?9] are homologous to those observed during the third trimester in human fetuses. In this study we sequentially (PDs 3, 5, 7) evaluated respiration rates in freely behaving unrestrained pups by whole body flow through plethysmography. The research was conducted in order to determine the net effects of a relatively high ethanol dose (3.0 g/kg, i.g.) upon neonatal respiration as well as the possibility that the magnitude of this autonomic response is regulated by stimuli that predict ethanol¢s effects. Hence, pups either received vehicle or 3.0 g-kg ethanol. These doses were preceded by no specific treatment or intraperitoneal administrations of vehicle or a 1.0 g/kg dose that in itself is not sufficient to alter respiration rates. At PD 9 all subjects were evaluated after being exposed to the stimuli that potentially signalled the effects of intragastric vehicle or the high ethanol dose. As expected, 3.0 g/kg ethanol resulted in all ages in a marked level of suppression of breathing frequencies. Of major importance was the observation that at PD9, stimuli that signalled the effects of this high ethanol dose generated isodirectional respiratory frequencies as those observed with 3.0 g/kg ethanol. This effect was particularly relevant when pups were re-exposed to a small ethanol dose (1 g/kg) and to a lesser extent, when exposed to i.p. administration of vehicle. No particular effects were observed in those pups in which no specific treatment preceded ethanol intoxication. These results strongly suggest that respiration depression originally generated by a high ethanol dose is reinstated by stimuli that are paired with such a dose. In light of the association existing between fetal alcohol exposure and sudden infant death syndrome, it is important to indicate that marked depressions in neonatal breathing patterns are likely to be elicited by stimuli originally associated with detrimental autonomic effects of relatively high ethanol doses experienced during early development.