Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

Abstract

This study used a rat model of Fetal Alcohol Syndrome to investigate whether combined prenatal and postnatal ethanol exposure affects met-enkephalin levels in the brains of male and female Long-Evans adult rats. Intragastric ethanol was administered to a group of rats (ET) from gestational day (GD) 1 through 22 and from postnatal day (PD) 2 through 10. The control groups consisted of a nontreated control group (NTC) and an intubated control group (IC) that received the intragastric intubation procedure but no exposure to ethanol. We measured met-enkephalin levels in the prefrontal cortex, nucleus accumbens, hypothalamus, central and basolateral nucleus of amygdala and ventral tegmental area. Met-enkephalin levels in the hypothalamus of male and female ET animals were significantly higher than those in either the NTC or IC animals. Metenkephalin levels in the central nucleus of the amygdala of male and female ET animals were significantly lower than the levels in the NTC animals. Met-enkephalin levels in the nucleus accumbens of ET females were significantly greater than those in the IC females. These results demonstrate that the combination of prenatal and postnatal ethanol exposure affects basal metenkephalin levels in specific regions in a sex-specific manner. These changes in met-enkephalin levels may explain how early ethanol exposure affects opioid-regulated behaviors such as social play, sexual behavior, and other social behaviors.

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: Possible mechanism for offspring ethanol overconsumption

“…This study provides the first evidence that prenatal exposure to ethanol, at 1 or 3 g/kg/day, stimulates expression of ENK specifically in the PVN and NAcC, but not the NAcSh, of postnatal offspring, consistent with studies showing a higher dose of ethanol (4.5 g/kg) to increase ENK levels in whole hypothalamus and accumbens of adolescent or adult offspring (Druse et al, 1999; Lugo et al, 2006). It additionally shows a similar increase in mRNA levels of GAL in the PVN and OX in the PFLH and reveals these effects both at birth and P15.…”

“…This evidence, suggesting the existence of a positive feedback loop in these brain sites (Morganstern et al, 2011), contrasts with that obtained in the arcuate nucleus (ARC), where GAL is unaffected by ethanol and neuropeptide Y (NPY) is negatively affected by ethanol (Barson et al, 2011). Whereas there are few studies of these peptide systems in offspring exposed in utero to ethanol, the evidence obtained so far shows that prenatal ethanol can stimulate the expression and levels of ENK in whole hypothalamus and NAc, as shown in preweanling and pubertal offspring (Druse et al, 1999; Lugo et al, 2006) but has little impact on NPY in whole hypothalamus (Dembele et al, 2006). These findings give some indication that the effects of prenatal ethanol on peptide expression in the offspring may be similar to those produced by ethanol intake in adult animals, raising the possibility that ethanol may alter in utero development of neurons expressing these orexigenic peptides known to stimulate ethanol drinking.…”

Activity and social behavior in a complex environment in rats neonatally exposed to alcohol

“…Such damage may contribute to the impaired impulse control and social deficits observed in children with FASD throughout life. In particular, rodent models of developmental alcohol exposure result in increased caspase-3 expression in the central nucleus of the amygdala (Mitchell & Snyder-Keller, 2003), long-term reductions to amygdalar opioid signaling (Lugo, Wilson, & Kelly, 2006), and altered synaptic connectivity and neuronal loss in the amygdala (Balaszczuk, Bender, Pereno, & Beltramino, 2011; Cullen et al, 2013; Zhou et al, 2010) and the prefrontal cortex (Hamilton, Whitcher, & Klintsova, 2010; Ikonomidou et al, 2000; Lawrence, Otero, & Kelly, 2012; Whitcher & Klintsova, 2008). Dysfunction of these brain areas could contribute to disruptions in social and play behavior observed in AE rats.…”

Selective effects of perinatal ethanol exposure in medial prefrontal cortex and nucleus accumbens

“…However, there clearly are changes in the neurochemical nature of the NAC after exposure to ethanol during development. For example, perinatal ethanol exposure resulted in an increase in Met-enkephalin levels in the nucleus accumbens of female but not male rats (Lugo et al, 2006b). Male rats exposed to ethanol during the prenatal period show elevated dopamine (DA) in the NAC following self-administered ethanol compared to controls; this effect was not seen in females (Blanchard et al, 1993).…”