Docosahexaenoic acid partially ameliorates deficits in social behavior and ultrasonic vocalizations caused by prenatal ethanol exposure

Abstract

Prenatal ethanol exposure disrupts social behavior in humans and rodents. One system particularly important for social behavior is the somatosensory system. Prenatal ethanol exposure alters the structure and function of this area. Docosahexaenoic acid (DHA), an omega 3 polyunsaturated fatty acid, is necessary for normal brain development and brains from ethanol-exposed animals are DHA deficient. Thus, we determined whether postnatal DHA supplementation ameliorated behavioral deficits induced by prenatal ethanol exposure. Timed pregnant Long-Evans rats were assigned to one of three groups: ad libitum access to an ethanol-containing liquid diet, pair fed an isocaloric isonutritive non-alcohol liquid diet, or ad libitum access to chow and water. Pups were assigned to one of two postnatal treatment groups; gavaged intragastrically once per day between postnatal day (P)11 and P20 with DHA (10 g/kg in artificial rat milk) or artificial rat milk. A third group was left untreated. Isolation-induced ultrasonic vocalizations (iUSVs) were recorded on P14. Social behavior and play-induced USVs were tested on P28 or P42. Somatosensory performance was tested with a gap crossing test around P33 or on P42. Anxiety was tested on elevated plus maze around P35. Animals exposed to ethanol prenatally vocalized less, play fought less, and crossed a significantly shorter gap than control-treated animals. Administration of DHA ameliorated these ethanol-induced deficits such that the ethanol-exposed animals given DHA were no longer significantly different to control-treated animals. Thus, DHA administration may have therapeutic value to reverse some of ethanol’s damaging effects.

The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: Insights from rodent models

“…While a three-trimester high-dose exposure has been shown to increase USV, a moderate dose over the same timespan did not (Marino, Cronise, Lugo, & Kelly, 2002; Ness & Franchina, 1990). Interestingly, a moderate first- and second-trimester exposure actually decreased USV (Wellmann, George, Brnouti, & Mooney, 2015). USV changes appear to be dependent upon dose as well as timing of exposure.…”

“…3). The majority of rodent studies show that aggressive play is decreased in adolescent and adult males across PAE exposures (Charles Lawrence, Cale Bonner, Newson, & Kelly, 2008; Kelly & Dillingham, 1994; Lugo, Marino, Cronise, & Kelly, 2003; Meyer & Riley, 1986; Wellmann et al, 2015). However, some studies have shown increases in wrestling behaviors in males (Hamilton et al, 2010, 2014; Royalty, 1990).…”

“…Studies show both increases and decreases in aggressive behaviors, using similar exposures and age of testing (Meyer & Riley, 1986; Royalty, 1990; Wellmann et al, 2015). Differences may be due to estrous cycle of the female at time of testing; however, none of the studies discussed here reported this variable.…”

“…Interestingly, it may be that moderate exposures are not enough to cause anxiety changes that are measurable on the elevated-plus maze (Barbaccia et al, 2007), but become evident on more stressful paradigms, such as gap crossing (Wellmann et al, 2015). As with the other domains, contrary findings have been reported, such as decreased anxiety on the zero maze using a moderate second- and third-trimester exposure (Cagiano et al, 2002).…”

Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats

“…Consequently, alcohol may become appealing to these individuals due to its ability to facilitate interactions with peers [20–22]. Social behavior of laboratory rodents is sensitive to prenatal ethanol exposure as well, with alterations in adolescent-characteristic [23–27] and adult-typical forms of social interactions [23, 28–30] evident following chronic fetal exposure to ethanol. Furthermore, our previous research has shown that in Long Evans rats prenatal exposure to a single, binge-like dose of ethanol on gestational day (G)12 (early neural generation), but not on G7 (gastrulation) or G15 (mid-neuronal generation), reproducibly results in sex- and age of testing-dependent social deficits.…”