Ethanol-exposed Rats Research Articles

Effects of maternal ethanol consumption and buspirone treatment on dopamine and norepinephrine reuptake sites and D1 receptors in offspring.

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.

Effect of calcium channel blocker diltiazem on some depressant actions of ethanol in UChA and UChB rats

Rats genetically selected for their different ethanol voluntary consumption, UChA (low consumer) and UChB (high consumer) were used. Naive UChA and UChB rats or submitted to ethanol chronic exposure, received an IP dose of ethanol (2.76 g/kg) alone or 30 min after an oral dose of diltiazem (10 mg/kg), a calcium channel blocker. A significant potentiation of the narcosis and hypothermia induced by the dose of ethanol was observed in UChA diltiazem-pretreated rats not previously exposed to ethanol, while no potentiation in narcosis time appears in UChA rats chronically exposed to ethanol that acquire tolerance. In the UChB line of rats, diltiazem did not potentiate ethanol depressant actions in naive or chronic ethanol-exposed rats. Diltiazem did not modify ethanol blood levels. These results indicate that the inhibition of voltage-dependent calcium channels can exagerate ethanol-induced effects in naive rats but not when tolerance was developed. Results suggest that UChB rats may have some innate tolerance that may be due to genetic difference in calcium channel function.

Fetal ethanol exposure alters pituitary-adrenal sensitivity to dexamethasone suppression.

The present study investigated the hypothesis that a deficit in feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the hormonal hyperresponsiveness seen in fetal ethanol-exposed rats. Male and female Sprague-Dawley rats from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) treatment groups were tested in adulthood. The effects of dexamethasone (DEX) blockade on basal and stress corticosterone (CORT) levels and stress adrenocorticotropin (ACTH) levels were examined over a 36-h period. Stress CORT and ACTH levels after DEX administration at the trough (AM) and peak (PM) of the CORT circadian rhythm were compared. DEX administration significantly suppressed both resting and stress levels of CORT and ACTH in all animals, regardless of prenatal treatment. Importantly, E animals did not differ from PF and C animals in basal CORT. However, E males and females had significantly higher stress levels of CORT and/or ACTH than PF and C animals, and further, showed differential responsiveness following DEX administration depending on the time of day when testing occurred. At the trough of the CORT circadian rhythm. E males did not differ from PF and C males, whereas E females had increased stress levels of CORT compared to PF and C females. In contrast, at the peak of the circadian rhythm, E males showed increased stress levels of CORT but not ACTH, whereas E females showed increased stress levels of both CORT and ACTH compared to males and females in respective control groups. These data support the hypothesis that E animals may exhibit deficits in HPA feedback inhibition compared to controls and suggest a sex-specific difference in sensitivity of the mechanism underlying HPA hyperresponsiveness.

Effects of chronic treatment with ethanol and withdrawal on levels of monoamines in rat cerebral cortex and striatum. Influence of midazolam, thiopenthal and somatostatin

It is accepted that ethanol affects the central neurotransmission. This paper deals with the effects of chronic ethanol treatment and withdrawal on cortical and striatal levels of several neurotransmitters. The influence of barbiturate, benzodiazepine and somatostatin has been studied in order to establish possible cross-interactions. Serotonin, 5-hydroxyindoleacetic acid, dopamine and norepinephrine levels from rat cerebral cortex and striatum were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Rats were chronically treated with ethanol (11–12 g/kg/day) for 6 weeks. The chronic ethanol treatment decreased the cortical serotonin ( P < 0.01) and 5-hydroxyindoleacetic acid ( P < 0.01) concentrations, while ethanol withdrawal decreased them in cortex and striatum. A single dose of different drugs produced an increase of serotonin and 5-hydroxyindoleacetic acid striatal—but not cortical—levels. The chronic ethanol treatment or 48 hr of ethanol-withdrawal produced a depletion of striatal serotonergic system when barbiturate thiopenthal was administered. The benzodiazepine midazolam elicited a decrease of striatal serotonin ( P < 0.01) and 5-hydroxyindoleacetic acid ( P < 0.05) levels in 48 hr ethanol-withdrawn and chronically ethanol-treated rats, respectively. Somatostatin injected to chronically ethanol-exposed rats resulted in decreased ( P < 0.05) striatal serotonin concentrations. Cortical norepinephrine levels decreased after 24 and 48 hr of ethanol-withdrawal ( P < 0.05 and P < 0.01, respectively). The depletion of striatal and cortical serotonergic systems after both chronic ethanol treatment and withdrawal, could be explained as an environment-dependent tolerance response. It can be concluded that ethanol and/or psychotropic drugs interact with neurotransmission systems in specific ways in different regions of the brain.

Beneficial effect of chronic nimodipine treatment on behavioral dysfunctions of aged rats exposed to perinatal ethanol treatment.

The long-term effects of prenatal and early postnatal ethanol exposure were assessed in adult (5-month), aged (24-month), and senescent (30-month) rats on non-aggressive intermale social behavior, and on black-white discrimination and spatial learning behaviors. Furthermore, the effects of chronic application of the Ca(2+) channel blocker nimodipine, which reportedly improves behavioral function in aging, were studied on the ethanol-induced behavioral deficits during aging. The results showed that the perinatal alcohol treatment suppressed social behavior by reducing the frequency and duration of social interactions at all ages. Black-white discrimination behavior and appetitively motivated learning in a hole-board were also markedly disturbed. Several measures of social and spatial learning behaviors of ethanol-exposed rats revealed progressive functional decline with aging. Chronic oral treatment with nimodipine improved the social activity and normalized the cognitive behavioral capabilities of aged and senescent rats exposed to ethanol. We concluded that: (1) the behavioral disabilities caused by perinatal ethanol toxicity are persistent in the rat lifespan and become more pronounced with aging; and (2) administration of nimodipine in the aging period improves, with a long-lasting efficacy, the ethanol-induced behavioral dysfunctions in aged rats.

Simultaneous changes in striatal dopamine, serotonin, and metabolites after withdrawal seizures in rats from dependence on alcohol

Ethanol dependence was achieved in male, Long-Evans rats after 8 days on a balanced liquid diet that supplied 4.5% ethanol. After 1-h access to a solution of 10% ethanol (95%)/5% sucrose, the rats were deprived of food, water, and ethanol for 9 h. Following 30-s key jingling, about 80% of the animals exposed to ethanol experienced tonic-clonic seizures. Neurochemical analyses of striatal tissues revealed a significant ( p < 0.05) increase in dopamine (DA) and a significant decrease in serotonin (5-HT) in the ethanol-exposed rats that had seizures compared to control rats. Homovaniilic acid concentrations of the ethanol-treated rats with seizures were significantly higher than the levels found in ethanol-treated animals that had experienced no seizures. Daily average ethanol intake of the rats that had seizures vs. those that did not was almost the same at 16 g/kg/day. The findings indicate that rats experiencing ethanol withdrawal-induced seizures manifest opposite alterations in dopaminergic and serotoninergic activity compared to controls. The present results do not reveal if the striatal changes are caused by ethanol rather than by the seizures.

Alterations in cortical visual evoked response following ethanol feeding in adult rats.

A study was performed on the visual-evoked response (VER) in adult rats that were given an ethanol containing liquid diet for 2 months and examined directly after the exposure period or subjected to a gradual decrease in ethanol over 3 days and total abstinence for 1 week. Control rats showed a first negative peak (N1) directly following the first positive peak (P1). In ethanol-exposed rats examined without withdrawal, the VER showed an increase in onset latency and a marked distorsion of the N1 region. The existing N1 potential was very sensitive to high-frequency stimulation. The alterations were partly normalized 1 week after withdrawal. There was no increase in latency to onset of the response or to P1. There remained an increase of latency and a reduced relative amplitude upon high-frequency stimulation of the N1 peak in ethanol-exposed rats compared with controls. The mechanisms underlying the changes in the cortical potentials are not clear, but they may be related to the cholinergic, glutamatergic/NMDA and/or noradrenergic cortical systems. The lack of persistent changes in onset and P1 latency may be related to the circumstance that the retinogeniculate impulses are transmitted over glutamatergic kainate receptors, which are relatively resistant to ethanol.

EFFECTS OF LIFELONG ETHANOL CONSUMPTION ON THE ULTRASTRUCTURE AND LIPOPIGMENTATION OF RAT HEART

The myocardial interactions of ageing and lifelong ethanol ingestion were studied in the ethanol-preferring AA (Alko Alcohol) line of rats. Samples of the left ventricle from young control rats (3-month), old control rats (30-month) and rats exposed to ethanol from 3 to 30 months of age, were studied in terms of myocardial ultrastructure and lipopigmentation. Electron microscopic morphometry showed an age-related increase in the volumetric densities of lipofuscin and unspecified sarcoplasm, while the proportions of mitochondria, myofibrils and tubular structures remained unaltered in the left ventricular myocardium. Lifelong ethanol exposure increased the proportion of sarcoplasmic reticulum and transverse tubules, apparently due to dilation of the tubular structures. Mitochondria were significantly larger in the ethanol-exposed rats compared to the control rats of the same age, while the volumetric proportion of mitochondria tended to decrease in the ethanol-exposed group. Fluorescence microscopic image analysis showed that myocardial lipopigmentation (proportion of myocardial area covered by autofluorescent lipopigments) was about two-fold in the old ethanol-exposed rats compared to the old control rats, and 13-fold compared to the young controls. It is concluded that ageing and chronic ethanol ingestion produce rather different patterns of alteration in myocardial ultrastructure, which does not support the concept of ethanol-induced accelerated ageing. The enhancement of myocardial lipofuscin accumulation is thought to reflect chronic oxidative stress in the hearts exposed to ethanol.

Postnatal high-peak blood ethanol concentration and external cue-based discrimination learning and reversal in the preweanling rat: comparison with memory-based discrimination learning.

Postnatal exposure to ethanol that produces high-peak blood ethanol concentrations (HP-BEC) in artificially reared infant rats affects hippocampal neuroanatomy and discrimination learning based on memorial cues from a patterned (single) alternation (PA) schedule in preweanling rats (P. L. Greene, J. L. Diaz-Granados, & A. Amsel, 1992). In the present experiments, discrimination by preweanling rats exposed to ethanol in the same way was tested with nonmemorial, external cues. In this external cue-based discrimination and in its reversal, ethanol-exposed rats were not different from normal or artificially reared controls whether the cues were presented in a PA or random manner, although there was some evidence that the memorial cues from the PA schedule contributed to learning a discrimination based on external cues, suggesting that the deficit reported earlier in ethanol-exposed rats is a memorial deficit and not a general discrimination deficit.

Prenatal ethanol exposure alters ethanol-induced dopamine release in nucleus accumbens and striatum in male and female rats.

Using in vivo microdialysis, ethanol-induced dopamine release in nucleus accumbens and striatum was examined in adult male and female Long-Evans rats exposed prenatally to ethanol and in controls. Following dialysis, ethanol intake was measured in an operant paradigm. Control rats showed increased dopamine release in nucleus accumbens and striatum in response to 0.5 g/kg ethanol, but not to 1.0 g/kg. Fetal ethanol-exposed rats showed no dopamine response at 0.5 g/kg. At 1.0 g/kg, fetal ethanol-exposed males showed increased dopamine release in both structures. Prenatally exposed females showed no change in accumbens, and decreased release in striatum. Fetal ethanol exposure did not significantly influence ethanol intake. The findings suggest that prenatal ethanol exposure influences subsequent neurochemical responses to ethanol; however, how these neurochemical measures are related to ethanol intake could not be determined in the present study. Data are discussed in terms of sex-specific shifts in the dose-response function for ethanol-induced dopamine release resulting from prenatal ethanol exposure.

Treatment of pregnant alcohol-consuming rats with buspirone: effects on serotonin and 5-hydroxyindoleacetic acid content in offspring.

This laboratory previously demonstrated that in utero ethanol exposure markedly impairs the development of the serotonergic system in rat brain. Developmental abnormalities could be detected as early as G15 in the brainstem and G19 in the cortex. Because of the importance of fetal serotonin (5-HT) and 5-HT1A receptors for the normal development of 5-HT containing neurons, we initiated studies to determine whether administration of a 5-HT1A agonist, buspirone, to pregnant rats could overcome the adverse effects of in utero ethanol exposure on the developing serotonergic system in offspring. Female, Sprague-Dawley rats were given daily subcutaneous injections of buspirone (4.5 mg/kg) from gestational day 13 (G13) to G20. 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content were determined in the cortex and cortical regions. These experiments demonstrated that the ethanol-associated abnormalities in the development of the serotonergic system can be partially overcome by in utero exposure to buspirone. Specifically, whereas untreated ethanol rats had a deficiency of 5-HT and/or 5-HIAA in whole cortex on PN5, and in the motor cortex on PN19 and 35, no significant differences were detected in these regions of the age-matched offspring of buspirone-treated, ethanol-fed rats. In contrast, the 5-HT and 5-HIAA deficiency in the somatosensory cortex of 19-day-old offspring of ethanol-fed rats was not corrected by in utero buspirone treatment. These results suggest that the abnormal development of cortical projections of serotonergic neurons may be due in part to the low fetal 5-HT content in ethanol-exposed rats and may potentially be overcome by in utero treatment with a 5-HT1A agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatostatin is altered in developing retina from ethanol-exposed rats

Optic nerve hypoplasia is seen in 50% of patients diagnosed with fetal alcohol syndrome and is due to a defect in the development of retinal ganglion cells. Somatostatin may influence the development of retinal ganglion cells, so we studied the effect of in vivo ethanol exposure on somatostatin expression in the developing retina. Somatostatin concentration is increased in retina from ethanol-exposed fetuses and pups and this increase in peptide is associated with excessive neurite formation and improper migration of the somatostatin-containing neurons at early postnatal ages. These disturbances may account for the eventual failure in retinal ganglion cell development that results in optic nerve hypoplasia.

Craniofacial Alterations in Adult Rats Prenatally Exposed to Ethanol

The rat was studied to determine whether gestational exposure to moderate amounts of ethanol produces permanent craniofacial malformations. Pregnant Long-Evans rats were fed a liquid diet containing 35% ethanol-derived calories or an isocaloric liquid diet between gestation days 6 and 20. Various dimensions of skulls and mandibles from adult male offspring were measured. All measurements taken in the parasagittal and coronal planes were significantly smaller in the ethanol-exposed rats than in the offspring of pair-fed controls. None of the vertical measurements was significantly altered. This report demonstrates that gestational exposure to ethanol in rats, at doses which produce lasting behavioral effects, also produces a specific constellation of craniofacial dysmorphisms without concomitant decreases in body weight.

β-Endorphin-immunoreactive neurons in the hypothalamus and medulla of the rat brain: Effect of prenatal ethanol

The number and distribution of β-endorphin neurons in the hypothalamus and medulla of rats is compared among three experimental treatment groups: prenatally ethanol-exposed rats, pair-fed control rats, and normally fed control rats. Quantitative analysis of β-endorphin-immunoreactive neurons in 12 sections through the rostral-caudal extent of the mediobasal hypothalamus revealed no significant difference in the total number or distribution of β-endorphin neurons among any of the three treatment groups. The mean number of β-endorphin neurons was consistently less in each of the 12 sections of pair-fed rats compared to normally fed rats, but there was no consistent difference between the mean number of neurons/section in prenatally ethanol-exposed rats compared to the normally fed controls. The distribution and time of appearance of a second population of β-en-dorphin neurons was analyzed in the caudal medulla. β-endorphin-immunoreactive neurons were easily visualized in the caudal medulla of rats from each treatment group on Postnatal Days 9–11. However, this population could not be identified with antisera against β-endorphin on Postnatal Days 19–21 in any treatment group, even though neurons in the hypothalamus of the same rats were easily visualized histochemically at this age. These data suggest that the well-characterized prenatally ethanol-induced alterations in central opioid systems cannot be attributed to changes in the number, distribution, or time of appearance of β-endorphin neurons in the brain.

Effect of ethanol on the distribution of cadmium between the cadmium metallothionein- and non-metallothionein-bound cadmium pools in cadmium-exposed rats

In an attempt to assess the effect of ethanol on cadmium accumulation, metallothionein (MT) synthesis, Cd-binding capacity and lipid peroxidation, rats were administered either Cd, ethanol or their combination for a period of 4 weeks. A significant increase in Cd accumulation was observed in all the organs of rats under study co-exposed to Cd and ethanol as compared to only Cd-treated rats. Increased MT levels in response to Cd were associated with a marked alteration in the distribution of Cd amongst the two pools of intracellular Cd i.e. Cd bound to MT (Cd-MT) and Cd not bound to MT (non-MT-Cd). Higher levels of non-MT-Cd were observed in liver, kidney and heart of Cd + ethanol-exposed rats as compared to only Cd-exposed rats. Lesser binding of 109Cd to the protein peak was observed in Cd + ethanol-exposed rats than the Cd-treated rats when hepatic supernatants from all the groups were chromatographed on Sephadex G-75 columns, suggesting that ethanol has a redistributing effect on Cd amongst the two pools. A marked increase in lipid peroxidation was observed which was linear to the increase in non-MT-Cd levels. A positive correlation between non-MT-Cd levels and lipid peroxidation was observed in liver, kidney and heart suggesting that non-MT-Cd levels are more crucial and toxicologically more important than total Cd levels.

Prenatal ethanol exposure during the last third of gestation in rat reduces hippocampal NMDA agonist binding site density in 45-day-old offspring

The effect of ethanol exposure during different periods of prenatal or postnatal development on hippocampal N-methyl-D-aspartate (NMDA) receptor binding was studied in rat. Fetal rat pups were exposed to ethanol for different periods of time during gestation via maternal consumption of a 3.35% ethanol liquid diet. In a separate experiment, neonatal pups were fed 2.51 g ethanol/kg body weight/day from Postnatal Day (PD) 4 to PD 10 via intragastric feeding tube. These two ethanol administration paradigms produced average peak maternal and pup blood ethanol concentrations of 39 mg/dl and 57 mg/dl, respectively. At 45 days of age, offspring from each treatment group were sacrificed for measurements of hippocampal NMDA-sensitive [ 3H]-glutamate binding site density using in vitro radiohistochemical techniques. As observed previously, prenatal ethanol exposure throughout gestation resulted in NMDA-sensitive [ 3H]-glutamate binding site reductions in the apical dendritic field regions of dentate gyrus, hippocampal CA 1 and subiculum of dorsal hippocampal formation compared to the ad lib or pair-fed control groups. NMDA-sensitive [ 3H]-glutamate binding was not different than control in rats exposed to ethanol during the first half of gestation only. Prenatal ethanol exposure during the last half or the last third of gestation resulted in NMDA-sensitive [ 3H]-glutamate binding site reductions comparable to the binding site reductions observed in rats exposed to ethanol throughout gestation. Hippocampal NMDA-sensitive [ 3H]-glutamate binding site density in postnatal ethanol-exposed rats was not different than the suckling or gastrostomy control groups. These results suggest that the critical period of vulnerability to ethanol-induced reductions in hippocampal NMDA receptor binding occurs during the last third of gestation in rat, which, in terms of human hippocampal development, is a period of time roughly equivalent to the fifth and six months of human gestation.

Carbohydrate-deficient transferrin in the ethanol-consuming rat model

Regular ethanol consumption leads to the appearance of carbohydrate-deficient transferrin in the plasma of human subjects. The mechanism for this finding remains uncertain. We have exposed female Wistar rats to ethanol from 3 weeks of age to 22 weeks and have studied transferrin in these animals. Isoelectric focusing (IEF) of serum identified two additional transferrin forms in the ethanol-exposed rats. Routine staining and immunofixation demonstrated transferrin focused at pH 5.45 and 5.65. Neuraminidase-treated normal rat serum focused in 2 bands at pH 5.85 and 6.15 corresponding to the additional bands in ethanol-treated rats. Human transferrin exposed to neuraminidase focused at pH 5.7 as described by others. The results suggest that the rat may be used as an animal model to study the complex effects of ethanol on transferrin and iron metabolism.

Craniofacial alterations in adult rats prenatally exposed to ethanol

The rat was studied to determine whether gestational exposure to moderate amounts of ethanol produces permanent craniofacial malformations. Pregnant Long-Evans rats were fed a liquid diet containing 35% ethanol-derived calories or an isocaloric liquid diet between gestation days 6 and 20. Various dimensions of skulls and mandibles from adult male offspring were measured. All measurements taken in the parasagittal and coronal planes were significantly smaller in the ethanol-exposed rats than in the offspring of pair-fed controls. None of the vertical measurements was significantly altered. This report demonstrates that gestational exposure to ethanol in rats, at doses which produce lasting behavioral effects, also produces a specific constellation of craniofacial dysmorphisms without concomitant decreases in body weight.

The effects of maternal ethanol exposure on neurotransmission and second messenger systems: a quantitative autoradiographic study in the rat brain

The effects of maternal ethanol exposure on neurotransmission and second messenger systems were examined in rats using histochemistry and in vitro autoradiography. Thirty % ethanol was administered to pregnant rats from gestational day 7 to the day of delivery. Quantitative autoradiography was used to map muscarinic cholinergic, dopamine D 2, adenosine A 1 and inositol 1,4,5-trisphosphate binding sites, as well as to localize adenylate cyclase and protein kinase C. We found no difference in the patterns of staining with acetylcholinesterase and Timm's stain between control and prenatally ethanol-exposed rats on postnatal day (PN) 30. In the ethanol-exposed rats, [ 3H]forskolin binding sites were increased during early development in the CA1 subfield of the hippocampus and the occipital cortex; [ 3H]phorbol ester binding sites were increased in the cortex, striatum, and hippocampus; hippocampal muscarinic cholinergic sites were increased on PN4 and 30; adenosine A 1 binding was reduced on PN10 in most regions examined, but was increased in the CA1 subfield on PN30; dopamine D 2 receptor levels were significantly reduced on PN30 in the striatum; and IP 3 receptors were decreased in most regions studied, but particularly in the cerebellum. Thus, some of these changes were transient and others were long-lasting. Although histophathological abnormalities were minimal, the alterations of binding sites in the cerebellum (the coordination center) and in the hippocampus (related to memory and learning) that were detected may contribute to the behavioral and mental deterioration seen in the fetal alcohol syndrome.

Effects of in Utero Ethanol Exposure on the Developing Serotonergic System

Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero.(ABSTRACT TRUNCATED AT 250 WORDS)