Dopamine, Serotonin, and Acid Metabolites in Brain Regions from the Developing Offspring of Ethanol‐Treated Rats

Abstract

Female rats were pair-fed control or ethanol liquid diets on a chronic basis prior to parturition. Six brain regions (hypothalamus, cerebellum, brain stem, cortex, corpus striatum, and hippocampus) were dissected from 19- and 35-day-old rat offspring for the determination of dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA). DA, 5-HT, and the acid metabolites were separated simultaneously by reverse-phase HPLC and were quantitated using electrochemical detection. Between 19 and 35 days of age in control rats we observed an increase in the concentration of 5-HT and 5-HIAA in the corpus striatum and hippocampus and a decrease in these compounds in the cerebellum. In addition, there was a development-related decrease of 5-HIAA in the hypothalamus and an increase in the brain stem. During the same age period the concentration of dopamine increased in the hypothalamus and corpus striatum. There was also a development-related decrease in the concentration of DOPAC in the corpus striatum and an increase in the cortex as well as a decrease in HVA in the cerebellum and cortex. In comparison to age-matched control animals the 19- and 35-day-old offspring of ethanol-treated rats had a lower concentration of 5-HT and/or 5-HIAA in the cortex, cerebellum, and brainstem. In addition the 35-day-old offspring of ethanol-treated rats exhibited a decrease in DA and HVA in the cortex. The results of the present study suggest that in utero ethanol exposure affects both the serotonergic and dopaminergic systems in brain.

Effects of Prenatal Ethanol Exposure on the Excitability of Ventral Tegmental Area Dopamine Neurons in Vitro

“…The electrical activity of DA neurons is critical in controlling the synthesis and release of DA (Gonon and Buda, 1985; SuaudChagny et al, 1992). Therefore, we suggest that prenatal ethanol exposure-induced reduction in the electrical activity of DA neurons could contribute to decreased DA function characterized in previous biochemical studies ( Rathbun and Druse, 1985;Cooper and Rudeen, 1988;Druse et al, 1990;Szot et al, 1999). …”

“…Impaired attention (Hausknecht et al, 2005) and dysfunctions of the mesolimbic/ cortical DA system are also observed in rats with prenatal ethanol exposure. Therefore, prenatal ethanol-exposed rats are a feasible animal model to study the neural mechanism of attention problems in individuals with FASDs.The prenatal ethanol exposure-induced dysfunctions in the mesolimbic/cortical DA system include reduced DA synthesis, uptake sites, receptor binding sites, and DA metabolites in both DA neuron cell body and terminal areas (Rathbun and Druse, 1985;Cooper and Rudeen, 1988;Druse et al, 1990;Szot et al, 1999). Dopaminergic neurons also have smaller cell bodies and retarded dendritic growth in prenatal ethanol-exposed animals (Shetty et al, 1993).…”

“…The prenatal ethanol exposure-induced dysfunctions in the mesolimbic/cortical DA system include reduced DA synthesis, uptake sites, receptor binding sites, and DA metabolites in both DA neuron cell body and terminal areas (Rathbun and Druse, 1985;Cooper and Rudeen, 1988;Druse et al, 1990;Szot et al, 1999). Dopaminergic neurons also have smaller cell bodies and retarded dendritic growth in prenatal ethanol-exposed animals (Shetty et al, 1993).…”

Methylphenidate Restores Ventral Tegmental Area Dopamine Neuron Activity in Prenatal Ethanol-Exposed Rats by Augmenting Dopamine Neurotransmission

“…For example, there is a reduction in DA uptake and receptor binding sites, DA content, and the DA metabolites in both the somatodendritic and terminal areas (Rathbun and Druse, 1985;Cooper and Rudeen, 1988;Druse et al, 1990) in prenatal ethanol-exposed animals. Prenatal ethanol exposure also can lead to changes in DA neuron morphology [e.g., smaller cell bodies and retarded dendritic growth in DA neurons (Shetty et al, 1993), DA receptor function (Shen et al, 1995;Wang and Shen, 2002), and DA receptor-mediated behavior (Hannigan and Randall, 1996)].…”

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

“…In fact, all known chemical inducers of autism including cocaine, thalidomide, valproate, and alcohol modulate 5-HT levels in the brain (Harris et al, 1995;Kramer et al, 1994;Narita et al, 2002;Rathbun and Druse, 1985;Stromland et al, 1994;Williams et al, 2001). A high proportion of children with autism exhibit elevated blood 5-HT levels (hyperserotonemia) and specific alterations in 5-HT biosynthesis.…”