Ontogeny of the enhanced fetal-ethanol-induced behavioral and neurophysiologic olfactory response to ethanol odor

Abstract

Background: Studies report a fundamental relationship between chemosensory function and the responsiveness to ethanol, its component orosensory qualities, and its odor as a consequence of fetal ethanol exposure. Regarding odor, fetal exposed rats display enhanced olfactory neural and behavioral responses to ethanol odor at postnatal (P) day 15. Although these consequences are absent in adults (P90), the behavioral effect has been shown to persist into adolescence (P37). Given the developmental timing of these observations, we explored the decay in the response to ethanol odor by examining ages between P37 and young adulthood. Moreover, we sought to determine whether the P15 neurophysiologic effect persists, at least, to P40.

Methods: Behavioral and olfactory epithelial (OE) responses of fetal ethanol exposed and control rats were tested at P40, P50, P60, or P70. Whole-body plethysmography was used to quantify each animal's innate behavioral response to ethanol odor. We then mapped the odorant-induced activity across the OE in response to different odorants, including ethanol, using optical recording methods.

Results: Relative to controls, ethanol exposed animals showed an enhanced behavioral response to ethanol odor that, while significant at each age, decreased in magnitude. These results, in conjunction with previous findings, permitted the development of an ontologic odor response model of fetal exposure. The fitted model exemplifies that odor-mediated effects exist at birth, peak in adolescence and then decline, becoming absent by P90. There was no evidence of an effect on the odor response of the OE at any age tested.

Conclusions: Fetal exposure yields an enhanced behavioral response to ethanol odor that peaks in adolescence and wanes through young adulthood. This occurs absent an enhanced response of the OE. This latter finding suggests that by P40 the OE returns to an ethanol "neutral" status and that central mechanisms, such as ethanol-induced alterations in olfactory bulb circuitry, underlie the enhanced behavioral response. Our study provides a more comprehensive understanding of the ontogeny of fetal-ethanol-induced olfactory functional plasticity and the behavioral response to ethanol odor.

Fig. 1

Ethanol effect size (mean ± SEM) at P40, P60, and P70. Relative to FC controls there was a 44% decline in the differential magnitude of the enhanced response to ethanol odor in ET animals between P40 and P70.

Fig. 2

Ontologic odor response model of fetal exposure. A single model of fetal ethanol-induced behavioral effects accurately fits: (i) the observation that a response to ethanol odor should be present at birth (e.g., Dominguez et al., 1998; Faas et al., 2000); (ii) P15 data from previous work (Youngentob and Glendinning, 2009), (iii) P40, P60, and P70 data from the current study, and (iv) the assumption of a nonsignificant effect of prenatal exposure at P90. Further, this model estimates that the enhancement of the behavioral response to ethanol odor peaks within late adolescence (approximately P45).

Fig. 3

Comparison by odorant and mucosal recording surface of the mean average response height as a function of maternal treatment. The magnitude of the mean average response (i.e., the height of the bars) is expressed in units of percent change in fluorescence (mean ± SEM). Septum (A) and turbinate (B) are illustrated for the P40 animals. For all test odorants, the responsivity of the OE was not altered as a function of prenatal treatment.