Neurotransmitter Systems

Abstract

Neurotransmitter systems have been long recognized as important targets of the developmental actions of alcohol (i.e., ethanol). Short­ and long­term effects of ethanol on amino acid (e.g., γ­aminobutyric acid and glutamate) and biogenic amine (e.g., serotonin and dopamine) neurotransmitters have been demonstrated in animal models of fetal alcohol spectrum disorders (FASD). Researchers have detected ethanol effects after exposure during developmental periods equivalent to the first, second, and third trimesters of human pregnancy. Results support the recommendation that pregnant women should abstain from drinking-even small quantities-as effects of ethanol on neurotransmitter systems have been detected at low levels of exposure. Recent studies have elucidated new mechanisms and/or consequences of the actions of ethanol on amino acid and biogenic amine neuro­ transmitter systems. Alterations in these neurotransmitter systems could, in part, be responsible for many of the conditions associated with FASD, including (1) learning, memory, and attention deficits; (2) motor coordination impairments; (3) abnormal responsiveness to stress; and (4) increased susceptibility to neuropsychiatric disorders, such as substance abuse and depression, and also neurological disorders, such as epilepsy and sudden infant death syndrome. However, future research is needed to conclusively establish a causal relationship between these conditions and developmental dysfunctions in neurotransmitter systems. KEY WORDS: Maternal alcohol exposure; prenatal alcohol exposure; fetal alcohol syndrome disorders; pregnancy; developmental disorders; central nervous system; neurotransmitter systems; amino acids; biogenic amines; animal models T his article reviews recent research on the short­ and long­term effects of developmental ethanol 1 (i.e., alcohol) exposure on brain chemical (i.e., neurotrans­ mitter) systems. The article focuses on studies that were per­ formed with tissue from animal models, including rats, mice, guinea pigs, and primates. It is noteworthy that prenatal development in rats and mice corresponds to the first and second trimesters of human pregnancy, whereas the first week of neonatal life corresponds to the third trimester. In guinea pigs and primates, intrauterine development more closely corresponds to the first, second, and third trimesters of human pregnancy. It also is important to keep in mind that the studies in this research area are quite heterogeneous in several respects, including the timing, duration, and route 1 The terms ethanol and alcohol are used interchangeably in this article. 106 Alcohol Research & Health of ethanol exposure; the levels of ethanol that were achieved in blood; and the techniques used to assess the effects of ethanol exposure. Regarding blood ethanol levels, it should be emphasized that the legal intoxication limit for driving is 0.08 g/dl and that, in some cases, developmental exposures to much higher ethanol levels were required to produce sig­ nificant effects (see table 1). Ethanol concentrations near 0.4 g/dl are typically lethal in individuals who do not regularly drink significant amounts of ethanol and have not developed tolerance to its depressant effects on brain activity. Therefore, care must be exercised when interpreting the results of studies that have used high concentrations of ethanol. This article first provides background information on neurotransmitter systems and their roles in normal central nervous system development and neurodevelopmental disorders. It then reviews studies on the actions of ethanol on two types of neurotransmitter systems: amino acids and biogenic amines. For the most part, the article reviews research published in the past decade. The reader is referred to more comprehensive review articles for additional information (Berman and