The interaction of gestational and postnatal ethanol experience on the adolescent and adult odor-mediated responses to ethanol in observer and demonstrator rats

Abstract

Background: Gestational ethanol exposure enhances the adolescent reflexive sniffing response to ethanol odor. Postnatal exposures of naïve animals as either an observer (i.e., conspecific) or demonstrator (i.e., intoxicated peer) using a social transmission of food odor preference paradigm also yields enhanced odor-mediated responses. Studies on the interaction of fetal and postnatal exposures using the social transmission paradigm have been limited to the responses of observers. When combined, the enhanced response is greater than either form of exposure alone and, in observer females, yields adult persistence. The absence of a male effect is noteworthy, given that chemosensory mechanisms are suggested to be an important antecedent factor in the progression of ethanol preference. Observers gain odor information on the breath of the demonstrator through social interaction. Demonstrators experience the pharmacologic properties of ethanol along with retronasal and hematogenic olfaction. Thus, we tested whether augmentation of the fetal ethanol-induced behavioral response with postnatal exposure as a demonstrator differed from that as an observer. We also examined whether re-exposure as a demonstrator yields persistence in both sexes.

Methods: Pregnant dams were fed an ethanol containing or control liquid diet throughout gestation. Progeny received four ethanol or water exposures: one every 48 hours through either intragastric infusion or social interaction with the infused peer beginning on P29. The reflexive behavioral sniffing response to ethanol odor was tested at postnatal (P) day 37 or P90, using whole-body plethysmography.

Results: When tested in either adolescence or adulthood - fetal ethanol exposed adolescent ethanol observers and demonstrators significantly differed in their odor-mediated response to ethanol odor both between themselves and from their respective water controls. Nonetheless, adolescent ethanol re-exposure as a demonstrator, like an observer, enhanced the reflexive sniffing response to ethanol odor at both testing ages by augmenting the known effects of prior fetal ethanol experience. At each age, the magnitude of the enhanced odor response in demonstrators was similar to that of observers. Interestingly, only re-exposure as a demonstrator resulted in persistence of the behavioral response into adulthood in both sexes.

Conclusions: The method of ethanol re-exposure plays an important role in prolonging the odor-mediated effects of fetal exposure. While ethanol odor-specific exposure through social interaction is important, additional factors such as the pairing of retronasal and hematogenic olfaction with ethanol's intoxicating properties appear necessary to achieve persistence in both sexes.

Fig. 1

Adolescent re-exposure model. Each prenatal treatment group provided 4 cages of same sex sibling pairs, 1 cage per sex for each of the adolescent exposure substances (ethanol or water). Within each pair, one animal was allocated as the demonstrator, receiving exposure through intragastric infusion (IG), and the other as the observer, receiving exposure through social interaction (SI).

Fig. 2

Behavioral index values (mean ± 2-dimensional SEM) for P37 fetal ethanol exposed observers and demonstrators that had been re-exposed to ethanol in adolescence. Ethanol observers and demonstrators responded differently to ethanol odor following adolescent re-exposure to the drug.

Fig. 3

Ethanol re-exposure effect size (mean ± SEM) of P37 fetal ethanol exposed animals as a function of mode of adolescent treatment. Both types of ethanol re-exposure led to similar magnitudes of behavioral enhancement as compared to their respective water controls.

Fig. 4

Behavioral index values (mean ± 2-dimensional SEM) for P90 fetal ethanol exposed observers and demonstrators that had been re-exposed to ethanol in adolescence. Ethanol observers and demonstrators differentially responded to ethanol odor when tested in adulthood as a consequence of their adolescent re-exposure experience.

Fig. 5

Ethanol re-exposure effect size (mean ± SEM) of P90 fetal ethanol exposed animals as a function of mode of adolescent treatment. On average, both modes of adolescent ethanol re-exposure resulted in an enhanced behavioral response to ethanol odor in adulthood.

Fig. 6

“Corrected” ethanol re-exposure effect size for P37 fetal ethanol exposed demonstrators (Ds - Corrected) as compared with the uncorrected effect sizes of both modes of treatment (i.e. observers and demonstrators (Ds - Uncorrected). The data are expressed as (mean ± SEM). When corrected for the hypothesized untoward effect of the intubation procedure, the magnitude of ethanol demonstrator re-exposure approximately doubles, making it roughly 3 times larger than the observer (odor exposure) effect.