Effects of alcohol exposure during development on play behavior and c-Fos expression in response to play behavior

Abstract

Developmental exposure to alcohol can produce characteristic physiological and cognitive deficits, often termed Fetal Alcohol Spectrum Disorder (FASD). More recently, social deficits have been shown to occur both in FASD and animal models of FASD; the behavioral and neural bases of these deficits remain to be determined. It was hypothesized that changes in sensory processing may in part underlie the social deficits seen in FASD. This study used a rat model of FASD and social play, a behavior critical to adult social functioning, to begin to examine this hypothesis. Somatosensory cues from dorsal contact to the nape of the neck, critical to the initiation of pinning, were systematically degraded by administration of different doses of xylocaine, a topical anesthetic. Neuronal activity after 1h of play was assessed by measurement of c-Fos immunoreactivity (IR) in different brain regions. Ethanol-exposed rats showed an increased frequency of pinning during social play and were more sensitive to the degradation of somatosensory cues compared to the control groups, suggesting difficulties in processing somatosensory cues. Neuronal activity in the somatosensory cortex induced by play was significantly decreased in the ethanol-exposed group compared to the non-treated group. The c-Fos IR in the nucleus accumbens was altered in a sexually dimorphic manner in the ethanol-exposed group. Thus, the behavioral and brain measures are consistent with the hypothesis that ethanol exposure during development induces alterations in social play via deficits in processing somatosensory cues that are important to social play.

Figure 1. Frequency of dorsal contacts

Ethanol treatment was without effect on dorsal contacts at all doses of xylocaine. Data are collapsed across sex. Error bars represent standard errors of the mean (SEM).

Figure 2. Frequency of Pinning

Ethanol treatment induced an elevation in pinning at 0, 0.5% and 1% xylocaine. While 2% xylocaine significantly reduced pinning in all groups, there was a greater effect of 2 % xylocaine in the ET group compared to both control groups. Data are collapsed across sex. Error bars represent SEM and stars indicate significantly different from both control groups at that xylocaine dose.

Figure 3. Effects of anesthesia on pinning by the two sexes

There was a significant interaction of anesthesia condition and sex but further analyses failed to reveal any specific effects within each sex. Data are collapsed across group. Error bars represent SEM.

Figure 4. c-Fos IR in the primary somatosensory cortex

C-Fos immunoreactivity in the somatosensory cortex of ET (n = 15), NC (n = 15), and IC (n = 16) animals (SH1, plates 48-52 [38]). Data are collapsed across sex. The star indicates a significant difference between ET group and the NC control. Error bars represent SEM.

Figure 5. Representative photomicrographs of c-Fos IR in the somatosensory cortex

c-Fos IR as seen in an NC (A), IC (B), and ET (C) animals are shown. Sections represent primary somatosensory cortex, shoulder region, corresponding to plates 48-52 [38].

Figure 6. c-Fos IR in the nucleus accumbens

A sexually dimorphic effect of ethanol on c-Fos IR in the nucleus accumbens (NAC, plates 16-18 [38]) was seen. ET females had significantly more c-Fos positive cells compared to IC females. ET males had significantly fewer c-Fos positive cells than NC males. Stars indicate a significant difference from one of the control groups. Error bars represent SEM. The subject numbers are 9, 7, and 7 in ET, IC and NC females respectively and 7, 7, and 9 in ET, IC and NC males respectively.

Figure 7. Representative Photomicrographs of c-Fos IR in the nucleus accumbens

C-Fos IR as seen in female NC (A), IC (C), and ET (E) animals and male NC (B), IC (D), and ET (F) animals.