Effects of Maternal Ethanol Consumption and Buspirone Treatment on Dopamine and Norepinephrine Reuptake Sites and D1 Receptors in Offspring

Abstract

Previously, it was shown that in utero ethanol exposure results in decreased serotonin (5-HT) and altered concentrations of 5-HT reuptake sites and 5-HT1A receptors in fetal and/or postnatal rats. Because fetal 5-HT is an essential trophic factor, this laboratory previously investigated the hypotheses that the early ethanol-associated 5-HT deficit contributed to subsequent development abnormalities in the serotonergic system and that the effects of the fetal 5-HT deficit could be prevented by maternal treatment with buspirone, a 5-HT1A receptor agonist. The present report determined the effects of maternal treatment with buspirone on two other neurotransmitter systems in the developing offspring of ethanol-fed dams: dopamine (DA) and norepinephrine reuptake sites and D1 receptors in postnatal day 19 offspring of control and ethanol-fed dams, that received daily injections of saline or 4.5 mg/kg buspirone. These investigations found that in utero ethanol exposure significantly decreased norepinephrine reuptake sites in the dorsomedial hypothalamic nucleus and anteroventral thalamic nucleus. There was also an ethanol effect in the dorsal raphe. D1 receptors were moderately increased (5-10% increase) in the striatum, and DA reuptake sites were unchanged in PN19 ethanol-exposed offspring. No other significant ethanol-related effects were noted. Maternal buspirone treatment did not adversely affect the concentration of DA reuptake sites or D1 receptors in control rats. Thus, whereas buspirone exerts protective effects on the developing 5-HT system of ethanol-exposed rats, it does not appear to damage the development of the DA system. Maternal buspirone produced only one significant abnormality in control offspring; it resulted in significant reduction of norepinephrine reuptake sites in the DR.

Alteration of selective neurotransmitters in fetal brains of prenatally alcohol‐treated C57BL/6 mice: quantitative analysis using liquid chromatography/tandem mass spectrometry

“…For example, in offspring prenatally exposed to ethanol, the concentration of norepinephrine was found to be lower in the brain overall, specifically in the hypothalamus, striatum, and septal areas (Detering et al, 1980a,b, 1981; Rudeen and Weinberg, 1993; Shoemaker et al, 1983). Another study has shown a significant decrease in norepinephrine reuptake sites in the dorsomedial hypothalamus nucleus and anteroventral thalamic nucleus of offspring that were prenatally exposed to ethanol (Gillespie et al, 1997). Based on these findings and our findings, we suggest that prenatal alcohol exposure induces a long‐lasting deficit in norepinephrine and possibly epinephrine.…”

In Utero Ethanol Exposure Increases Proenkephalin, a Precursor of a Neuropeptide That Is Inhibitory to Neuronal Growth

“…These brain regions were examined because of their importance to motor function (Angulo and McEwen, 1994;Dauge et al, 1988Dauge et al, , 1992Fallon and Leslie, 1986;Kalivas and Duffy, 1990), their sensitivity to the effects of in utero ethanol exposure (Blanchard et al, 1993;Detering et al, 1980;Druse et al, 1990;Gillespie et al, 1997), and their high concentration of PE mRNA and PE peptide (Fallon and Leslie, 1986). PE mRNA was measured in the rostral and caudal striatum and in the nucleus accumbens, and PE peptide was quantified in striatum and nucleus accumbens.…”

Fetal alcohol spectrum disorders and cognitive functions of young children

“…Previous studies showed that alcohol may reduce both the size and the spontaneous activity of dopaminergic neurons (Detering et al, 1980;Cooper and Rudeen, 1988;Druse et al, 1990;Shetty et al, 1993). Antenatal ethanol exposure also affects dopamine-1 receptors, which are decreased in certain brain areas such as the striatum (Gillespie et al, 1997;Shen et al, 1999). Experimental animal studies suggested that ethanol exposure during the early antenatal period reduces dopaminergic function during adulthood, whereas late ethanol exposure results in an exactly opposite effect (increment of dopaminergic function) (Schneider et al, 2005).…”