Bcl-2 overexpression protects the neonatal cerebellum from ethanol neurotoxicity

The developing nervous system is extremely sensitive to ethanol, and exposure often produces a condition known as the fetal alcohol syndrome. Although mechanisms underlying developmental ethanol toxicity have long been sought, they remain poorly understood. In this study, we examined the ability of the cell death repressor gene bcl-2 to protect against ethanol neurotoxicity. Transgenic mice overexpressing bcl-2 in neurons were exposed to ethanol vapor on postnatal days 4 and 5, which is the peak period of vulnerability of cerebellar Purkinje cells to ethanol. While exposure of wild-type animals to ethanol resulted in significant loss of Purkinje cells by P5, similar exposure of homozygous and heterozygous transgenics had no effect on the number of these neurons. This study suggests that bcl-2 can protect neurons from ethanol neurotoxicity and that modulation of cell death effector or repressor gene products may play a significant role in developmental ethanol neurotoxicity.     

Prenatal Alcohol Exposure Causes Attention Deficits in Male Rats.

Children with fetal alcohol spectrum disorder (FASD) are often diagnosed with attention-deficit/ hyperactivity disorder (ADHD). These children show increases in reaction time (RT) variability and false alarms on choice reaction time (CRT) tasks. In this study, adult rats prenatally exposed to ethanol were trained to perform a CRT task. An analysis of the distribution of RTs obtained from the CRT task found that rats with a history of prenatal ethanol exposure had more variable RT distributions, possibly because of lapses of attention. In addition, it was found that, similar to children with FASD, the ethanol-exposed rats had more false alarms. Thus, rats with prenatal ethanol exposure show attention deficits that are similar to those of children with FASD and ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The indoor air and children''s health study: methods and incidence rates

The effect of chronic alcohol (33 mM ethanol) on Ca2+ signals elicited by glutamate receptor agonists (quisqualate and NMDA) was examined in developing cerebellar Purkinje and granule neurons in culture. The neurons were exposed to alcohol during the second week in culture, the main period of morphological and physiological development. The Ca2+ signals were measured with fura-2 based microscopic video imaging. Chronic exposure to alcohol during development significantly reduced the peak amplitude of the Ca2+ signals to quisqualate (1 microM; Quis) in both the somatic and dendritic regions of the Purkinje neurons. The dendritic region was affected to a greater extent than the somatic region. Granule neurons also showed a reduced somatic Ca2+ signal to Quis (dendrites not measured) in the alcohol-treated cultures, indicating that the effect was not limited to Purkinje neurons. In addition to the effects on in the response to Quis, the peak amplitude of the Ca2+ signals to NMDA (100 microM) was reduced by chronic alcohol exposure during development in both the cultured Purkinje and granule neurons. Resting Ca2+ levels were not consistently affected by alcohol treatment in either neuronal type. These results indicate that Ca2+ signaling linked to glutamate receptor activation is an important target of alcohol in the developing nervous system and could be a contributing factor in the altered CNS function and development observed in animal models of fetal alcohol syndrome.     

Influence of chronic prenatal ethanol on cholinergic neurons of the septohippocampal system

This study characterized the influence of full-term gestational ethanol exposure on choline acetyltransferase (ChAT)-immunoreactive neurons that project to the hippocampus, within the medial septal (MS) nucleus and the vertical limb of the diagonal band of Broca (DBv). On gestation days 1-22, pregnant dams were fed either a vitamin fortified ethanol-containing liquid diet, pair fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In a previous study, we found that chronic prenatal exposure to ethanol, in this manner, resulted in a significant decline in the ontogenetic upregulation of ChAT activity in the septal area during the second postnatal week, but was followed by recovery to control levels by adulthood. On postnatal days 14 and 60 (P14 and P60) the brains were prepared for ChAT immunocytochemistry. Ethanol exposure had little influence on the number of ChAT-positive neurons in the MS nucleus of animals at either age. Ethanol exposure had no effect on neuronal size or ChAT staining intensity of MS or DBv neurons when compared to chow-fed offspring. Although age-related increases in cholinergic neuronal numbers and decreases in neuronal size were observed between juvenile and adult animals, prenatal ethanol exposure did not appear to influence these postnatal changes in the population as a whole. Overall, these findings suggest that the anatomical maturation of septal cholinergic neurons may be relatively insensitive to prenatal ethanol exposure under conditions of a vitamin-rich dietary supplementation, while biochemical development within this region may be more susceptible to early ethanol influences.     

A comparison of patient recovery following unilateral and bilateral endoscopic preperitoneal herniorrhaphy

This study examined the effects of prenatal ethanol exposure on hippocampal theta activity in adult rats. Subjects were randomly selected from four prenatal treatment conditions: untreated, 0, 3, or 5 g/kg/day ethanol. At approximately 90 days of age, all subjects were surgically implanted with a bipolar electrode in the CA1 region of the hippocampus. Four epochs of hippocampal theta rhythm activity were recorded while the subjects were moving and four more while still, and a normalized theta score was computed and compared among groups. The 5 g/kg male group demonstrated a significantly higher theta score than controls, indicating either an increase in type I (movement-associated) theta and/or a decrease in type II (information-processing) theta activity. These results are consistent with prior reports that prenatal ethanol exposure alters hippocampal function and support clinical indications that monitoring the EEG of children may prove to be useful in the diagnosis of fetal alcohol syndrome and/or the detection of alcohol-related birth defects.     

Maternal adrenalectomy eliminates a surge of plasma dehydroepiandrosterone in the mother and attenuates the prenatal testosterone surge in the male fetus

Previous work has established a number of sex-related deficits in immune function, behavior, and endocrine responses to stress in the offspring of dams exposed to ethanol. To examine the potential role of maternal glucocorticoids as a mediator of these sexually dimorphic effects in the fetus, we examined the influence of prenatal alcohol exposure in the presence or absence of maternal glucocorticoids on fetal plasma corticosterone (CORT) production. An additional question to be addressed by these studies was whether maternal adrenalectomy could eliminate the known inhibition by ethanol of the prenatal surge of plasma testosterone in male fetuses. Pregnant dams were adrenalectomized (ADX) or sham-adrenalectomized on gestational day (G) 7 and placed on a liquid diet containing 35% ethanol-derived calories or pair-fed an isocaloric control diet throughout the experiment. On G18, G19, and G21, plasma levels of CORT, testosterone, and dehydroepiandrosterone (DHEA) were measured in male and female fetuses and their mothers. Ethanol administration consistently increased maternal plasma CORT levels but did not significantly alter CORT levels in the fetus. Maternal ADX resulted in compensatory increases in fetal CORT levels that were lower in fetuses of ADX dams on alcohol, suggesting a direct effect of ethanol on fetal pituitary-adrenal activity. There were no significant sex differences in fetal plasma CORT levels in response to any of these manipulations. A novel surge of maternal plasma DHEA was found on G19 that was absent in plasma from ADX dams. In spite of the absence of a surge on G19, plasma DHEA levels of ADX dams rose from very low levels at G18 to levels on G21 that were significantly higher than in Sham dams. A normal testosterone surge was observed in male fetuses on G18 and G19 from sham-adrenalectomized dams administered the pair-fed diet. However, this surge was greatly attenuated in males administered ethanol and also in male fetuses from ADX dams. These results reveal a direct inhibitory influence of ethanol on fetal CORT secretion as well as on the prenatal testosterone surge in males. Furthermore, these studies demonstrate the presence of a surge of DHEA in the pregnant rat. Overall, these data suggest that there is a critical adrenal factor in the rat that regulates the maternal surge of DHEA on G19 and the prenatal testosterone surge of male fetuses on G18-19.     

Prenatal ethanol exposure alters neurotrophic activity in the developing rat hippocampus

Extract made from hippocampus of rat pups exposed prenatally to an ethanol-supplemented diet was found to contain more neurotrophic activity at postnatal day 21 than that from animals exposed to control diets, when quantified in a dorsal root ganglion bioassay. This apparent upregulation was specific to hippocampal extract (cerebellar and forebrain/midbrain extracts were also assessed), and to this age (P1, P7, P14 and P60 extracts were also tested). It was suggested that this upregulation may be indicative of, or secondary to, trauma resulting from fetal ethanol exposure. It is speculated that such departures from the normal developmental timetable could contribute to anomalies seen in the fetal alcohol syndrome.     

Effect of prenatal exposure to ethanol on intestinal development of rat fetuses

BACKGROUND: Chronic alcoholism in pregnant animals and humans lead to general growth impairment in their offspring, which show multiple birth defects and delayed grown (fetal alcohol syndrome). Here we study the maturation of the intestine under the effect of chronic exposure to ethanol in utero together with associated malnutrition. METHODS: Lactase, acid beta-galactosidase, maltase, and alkaline phosphatase activity profiles were monitored in 18-, 19-, 20-, and 21-day-old fetuses from rats kept under three nutritional treatments before and during gestation: alcohol-treated (25% ethanol in drinking water), fiber-treated (50% cellulose-diluted diet) as a control of the malnutrition associated with chronic alcoholism, and control or normal diet. Serum corticosterone determination and lactase immunolocalization were carried out. To detect possible direct effects of ethanol during the period of mucosa development, intestinal explants from 18-, 19-, and 20-day-old control fetuses were cultured either in the basal medium alone or in a medium containing 25 mM ethanol for 72, 48, and 24 h of incubation, respectively. RESULTS: Following chronic ethanol exposure in utero, intestinal weight and brush-border protein content and the specific activities of lactase, acid beta-galactosidase, maltase, and alkaline phosphatase were significantly lower than those of nutritional controls. Organ culture results, under the assay conditions stated, did not show a direct effect of ethanol 25 mM on prenatal mucosal functionality. CONCLUSIONS: All these results suggest that maternal malnutrition is not primarily responsible for the impaired intestinal maturation in rat fetuses from alcohol-treated mothers; indirect effects of ethanol and/or its derivatives throughout embryo-fetal development could be necessary to promote this intestinal delay.     

The effect of gestational ethanol exposure on voluntary ethanol intake in early postnatal and adult rats.

Clinical and epidemiological studies provide strong data for a relationship between prenatal ethanol exposure and the risk for abuse in adolescent and young adult humans. However, drug-acceptance results in response to fetal exposure have differed by study, age at evaluation, and experimental animal. In the present study, the authors tested whether voluntary ethanol intake was enhanced in both the infantile and adult rat (15 and 90 days of age, respectively), as a consequence of chronic fetal drug experience. Experimental rats were exposed in utero by administering ethanol to a pregnant dam in a liquid diet during gestational Days 6-20. Compared with those for isocaloric pair-fed and ad lib chow control animals, the results for experimental animals demonstrated that fetal exposure significantly increased infantile affinity for ethanol ingestion without affecting intake patterns of an alternative fluid (water). Heightened affinity for ethanol was absent in adulthood. Moreover, the results argue against malnutrition as a principal factor underlying the infantile phenomenon. These data add to a growing literature indicative of heightened early postnatal acceptance patterns resulting from maternal use or abuse of ethanol during pregnancy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experience-induced fetal plasticity: The effect of gestational ethanol exposure on the behavioral and neurophysiologic olfactory response to ethanol odor in early postnatal and adult rats.

Human fetal ethanol exposure is strongly associated with ethanol avidity during adolescence. Evidence that intrauterine olfactory experience influences chemosensory-guided postnatal behaviors suggests that an altered response to ethanol odor resulting from fetal exposure may contribute to later abuse risk. Using behavioral and neurophysiological methods, the authors tested whether ethanol exposure via the dam's diet resulted in an altered responsiveness to ethanol odor in infant and adult rats. Compared with controls, (a) fetal exposure tuned the neurophysiologic response of the olfactory epithelium to ethanol odor at some expense to its responsiveness to other odorants in infantile rats--this effect was absent in adults; (b) the neural effect in infantile rats was paralleled by an altered behavioral response to ethanol odor that was specific to this odorant--this effect was also absent in adults; and (c) a significant component of the infantile behavioral effect was attributable to ethanol's effect on the olfactory neural modality. These data provide evidence for an important relationship between prenatal ethanol experience and postnatal behavioral responsiveness to the drug that is modulated or determined by olfactory function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute alcohol exposure markedly influences male fertility and fetal outcome in the male rat

Although it is recognized that drugs ingested by pregnant females produce marked cognitive and physiological deficits in their offspring, the possibility that paternal exposure to drugs prior to mating may have adverse effects on fertility and fetal outcome has not received much attention. The purpose of the present studies was to examine whether a single, acute exposure to alcohol influences the subsequent ability of adult male rats to mate and produce healthy and viable litters. Our results showed that a relatively large dose of alcohol 24 hours prior to breeding had little effect on the mating behavior of male rats, but there were markedly fewer pregnancies in females mated with alcohol-exposed male rats than in controls. Of equal importance, we found that, even when conception occurred and live births were produced, there were striking differences in fetal outcome. Alcohol-treated males sired many fewer pups than control males and there was a markedly enhanced mortality rate in their offspring. Collectively, these data suggest that acute paternal alcohol administration 24 hours prior to breeding does not affect mating behavior, but results in a greatly diminished fertility rate and fewer and less viable offspring. These studies suggest that paternal alcohol use may be as important as maternal alcohol abuse as a negative variable in pregnancy and fetal outcome.     

Prenatal ethanol exposure differentially alters behavior in males and females on the elevated plus maze

Rodents prenatally exposed to ethanol demonstrate hypothalamic-pituitary-adrenal and behavioral hyperactivity to a variety of stressful situations. The present study examined both behavioral and corticosterone (CORT) responses to the elevated plus maze (+-maze), an anxiety- or fear-provoking task. Sprague-Dawley male and female offspring from fetal ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were tested at 60 to 90 days of age. In experiment 1, behavior was measured in animals exposed to the +-maze for 5 min on two consecutive days; 2 weeks later, both behavioral and CORT responses were measured in animals confined to the open and closed arms of the maze for 20 min. In experiment 2, animals were placed in an open field (OF) for 5 min before a single 5-min exposure to the +-maze. Factor analysis of the scored behaviors from the two experiments indicated two main factors, designated "exploration" and "fear." E males and females both exhibited higher levels of exploratory behaviors when placed directly on the +-maze from their homecages without prior exposure to the OF, compared with C males and females. In addition, when confined to the closed arms of the +-maze, E males and females demonstrated higher levels of activity, compared with C males and females. After OF exposure, however, both E males and females demonstrated lower levels of exploratory behaviors than C males and females, and E females also had increased CORT levels, compared with PF and C females. Interestingly, E females, but not E males, showed an increase in fear-related behaviors on the +-maze, compared with controls, regardless of prior OF exposure. These data demonstrate that prenatal ethanol exposure may differentially affect both behavioral and hormonal responses of males and females in an aversive behavioral task and suggest that there may be a sex difference in the sensitivity of the mechanism(s) underlying these responses.     

Choline supplementation following third-trimester-equivalent alcohol exposure attenuates behavioral alterations in rats.

Despite the known adverse consequences of prenatal alcohol exposure, some pregnant women continue to drink alcohol, making it imperative to identify treatments for children with fetal alcohol spectrum disorders. The authors recently reported that perinatal choline supplementation can reduce some fetal alcohol effects (J. D. Thomas, M. Garrison, & T. M. O'Neill, 2004), and the present study examined whether choline supplementation is effective when administered after third-trimester-equivalent ethanol treatment. Rat pups were exposed to 6.0 g/kg/day ethanol during the neonatal brain growth spurt (Postnatal Days [PD] 4-9) and treated with choline chloride (0, 10, 50, or 100 mg/kg) from PD 10-30. Behavioral testing occurred after choline treatment had ceased. Female subjects exposed to ethanol were overactive and exhibited spatial learning deficits, effects that were attenuated with all doses of choline supplementation. These data indicate that choline supplementation can alter brain development following a developmental insult. Moreover, the data suggest that early dietary interventions may reduce the severity of some fetal alcohol effects, even when administered after birth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The plant 2-Cys peroxiredoxin BAS1 is a nuclear-encoded chloroplast protein: its expressional regulation, phylogenetic origin, and implications for its specific physiological function in plants

Although it is well known that lead (Pb2+0 acutely blocks voltage-gated calcium currents (VGCCs) in mammalian neurons, little is known about the long-term effects of continuous exposure to this metal on VGCCs. In the present study, the effects of chronic lead exposure on VGCCs (with barium ions as the charge carrier) were studied using whole-cell patch-clamp electrophysiological techniques in acutely dissociated medial septum (MS)/nucleus diagonal band (nDB) neurons. Neither peak, end current amplitudes, nor the current-voltage relationship were affected by chronic lead exposure. However, VGCCs repetitively evoked at frequent 6 s intervals displayed diminished whole-cell current rundown after 2 min of stimulation in cells from chronic Pb-exposed rats compared to cells from control Na-exposed rats. Because rundown after repetitive stimulation at a slower rate (20 s intervals) was not different between Pb-exposed and Na-exposed, reduced rundown at 6 s intervals was probably due to decreased slow inactivation of voltage-gated calcium channels. Interestingly, acute application of 60 mM ethanol reversed the reduced rundown in cells from Pb-exposed rats while having no effect on cells from Na-exposed rats. Clearly, acute ethanol treatment antagonized the effect of chronic lead exposure, unlike the additive interaction we observed previously with synaptic plasticity (Grover and Frye, 1996). Acute application of 1 microM Pb2+ completely blocked VGCCs similarly in neurons from Na-exposed and Pb-exposed rats. These findings do not suggest that major adaptive changes in VGCCs have occurred during chronic in vivo exposure to lead. But, subtle changes in channel efficiency only revealed under conditions of repetitive stimulation may exist, and are reversed by ethanol. These subtle changes may be sufficient to influence neuroplasticity such as LTP.     

Influences of gender, development, pregnancy and ethanol consumption on the hematotoxicity of inhaled 10 ppm benzene

The hematotoxic effects of benzene in both humans and animals are well documented. Current estimates concerning the risks associated with benzene exposure are usually based on adult, male cohort studies; however, there are indications that females may respond differently than males to benzene and that fetuses may respond differently than adults. Another factor to be considered in risk estimates is the impact of personal habits. In experimental animals, ethanol consumption is known to increase the hematotoxicity of benzene; therefore, alcohol consumption may also alter the potential risk of individuals exposed to benzene. To address some of the factors that may confound risk estimates for benzene exposure, a series of experiments were performed. Age-matched male as well as pregnant and virgin female Swiss Webster mice were exposed to 10 ppm benzene for 6 h a day over 10 consecutive days (days 6 through 15 of gestation for the pregnant females). Half of the animals also received 5% ethanol in the drinking water during this period. On day 11, bone marrow cells from the adults and liver cells from the fetuses were assayed for the numbers of erythroid colony-forming units (CFU-e). CFU-e assays were also performed on bone marrow cells isolated from 6-week postpartum dams exposed during gestation and from in utero-exposed 6-week old males and females. Gender differences were clearly observed in the responses to the various exposure protocols. Depressions in CFU-e numbers were only seen in male mice while elevations in CFU-e numbers were only seen in female mice. Male mice exposed as adults for 10 days to benzene (B), ethanol (E) or benzene+ethanol (B+E) exhibited depressed CFU-e levels as did male fetal mice exposed to B in utero. In addition, adult male mice which had been exposed in utero to either B or to E individually displayed depressed CFU-e levels. In contrast, none of the groups of female mice exhibited any depressions in CFU-e numbers after any of the exposures. Elevations in CFU-e numbers were observed among pregnant females exposed to E and among adult females exposed to B+E in utero. In summary, a majority (6/9) of the exposure protocols produced depressions in the CFU-e numbers of male mice, whereas a majority (7/9) of the exposure protocols produced no changes in the CFU-e numbers of female mice. Those changes that were observed in females consisted of elevations of CFU-e numbers. These results suggest that the male erythron is more susceptible than the female erythron to the hematotoxicants benzene and ethanol, regardless of whether exposures occur in utero or during adulthood.     

Effects of maternal ethanol consumption in rats on basal and rhythmic pituitary-adrenal function in neonatal offspring

Neonatal corticoid treatment delays development of the circadian rhythm of plasma corticosterone in rats. We therefore sought to determine whether fetal or neonatal exposure to ethanol, a substance which activates the hypothalamo-pituitary-adrenal axis, produces similar effects. Subjects were the offspring of dams fed a 5.0% w/v ethanol-containing liquid diet or pair-fed an isocaloric control diet during gestation weeks two and three or during postnatal week one. At birth (day 1), the fetal ethanol-exposed pups had significantly higher brain and plasma corticosterone levels than the pair-fed or normal controls; brain and body weights were unaffected. By day 3, brain and plasma corticosterone titers in the fetal ethanol-exposed pups declined to the levels of the pair-fed and normal controls, although brain weights were significantly reduced. Significantly higher p.m. than a.m. levels of plasma corticosterone first occurred on day 18 both in the fetal ethanol-exposed pups and in the pair-fed and normal controls. Thus, despite its causing elevated corticosterone levels at birth, fetal exposure to ethanol did not affect the onset of the pituitary-adrenal circadian rhythm. On the other hand, exposure to ethanol during the first neonatal week delayed the onset of the pituitary-adrenal rhythm from day 18 to day 21. However, even greater delays occurred in the neonatal pair-fed controls, suggesting that the delays following neonatal exposure were due to nutritional deficits rather than to alcohol per se. The developmental and long-term influences of elevated corticoid levels at birth in fetal ethanol-exposed rats on other aspects of pituitary-adrenal function remain to be determined.     

Alcohol/"low-dose" carbon tetrachloride-induced cirrhosis in rats using different methods of alcohol feeding

Cirrhosis may be reliably produced in rats by exposing them to low levels of carbon tetrachloride vapor while feeding alcohol in the Lieber-DeCarli liquid diet. This study aimed to determine whether alternative cheaper and more convenient ways of feeding alcohol would also allow the production of cirrhosis. Animals were fed alcohol in the Lieber-DeCarli diet, in a gel diet, or by addition of alcohol + sucrose to their drinking water, and were exposed to carbon tetrachloride vapor 6 hr/night, 5 nights/week. After 12 weeks of treatment, all animals (4 of 4) receiving alcohol in the Lieber-DeCarli diet, but only two in each of the gel and drinking water groups, were cirrhotic. The variable results with the gel diet may be due to loss of alcohol by evaporation from the gel. Alcohol intake in the group receiving alcohol in drinking water was greater than in those receiving Lieber-DeCarli diet. We suggest that the increased carbohydrate intake due to addition to sucrose to the water exerted a protective effect on the liver.     

Induction of Fos-like proteins and ultrasonic vocalizations during ethanol withdrawal: further evidence for withdrawal-induced anxiety

The ethanol withdrawal syndrome includes anxiety as a prominent symptom. Because the extent that specific regions of brain are critical to the generation of this emotional state is unknown, Fos-like immunoreactivity (Fos-LI) was used to associate specific regions of the rat brain with the anxiety component of the ethanol withdrawal syndrome exacerbated by an air puff challenge in rats. Chronic ethanol liquid diet was administered intragastrically for 4 days or by having the rats consume the diet for 14 days. During withdrawal from either treatment protocol, Fos-LI was induced most prominently in forebrain areas, although the midbrain and hindbrain were also represented. Included in these Fos-LI positive regions were many cortical regions, septum, accumbens, claustrum, amygdala, paraventricular nucleus of the thalamus and hypothalamus, hippocampus, locus coeruleus, and central gray. Fos-LI expression differed mostly in intensity between the two treatment and withdrawal protocols, with the gastric protocol producing the greatest Fos-LI induction in most brain regions. The threshold for air puff-induced ultrasonic vocalizations was decreased, and the number of vocalizations was increased and the period of vocalization was extended. These behavioral data indicate that aversively motivated responding in rats during ethanol withdrawal can be readily quantified with the ultrasonic vocalizations test without precipitating convulsive activity. Furthermore, a comparison of the effects of the air puff challenge versus withdrawal on Fos-LI indicated that the behavioral state induced in these two situations share functional neuroanatomical features. Some regions--such as the accumbens core, medial septum, subregions of the amygdala, hippocampus, substantia nigra, and cerebellum--exhibited little Fos-LI during withdrawal and also did not exhibit strong increases after the addition of the air puff challenge. However, other regions-such as the cerebral cortex (medial prefrontal, frontal, cingulate and ventrolateral orbital, claustrum, and tenia tecta), hypothalamus, and locus ceoruleus- exhibited Fos-LI at levels higher than that seen after either the ethanol withdrawal or puff challenge alone. These overlapping patterns of Fos-LI in specific regions of the brain, activated by both ethanol withdrawal and an anxiety provoking behavioral challenge, suggest that specific neuroanatomical sites in brain are associated with the symptom of anxiety observed during the "ethanol withdrawal syndrome."     

Effects of prenatal alcohol exposure on the postnatal morphology of the rat oculomotor nucleus

Morphological development of the rat oculomotor nucleus was investigated on postnatal day 15 following a prenatal ethanol exposure. Analysis of toluidine blue stained plastic sections showed that the prenatal alcohol exposure caused a decrease in the density of neurons and an increase in the density of astrocytes in the center of the nucleus. There was an alcohol-induced reduction in the overall size of the cross-sectional region of the oculomotor nucleus, but no effect on the number of neurons per unit area of that total oculomotor region, indicating a delay or alteration of the migration of neurons to their normal clustered position in the center of the nucleus. The areas of the neuronal cell nucleus and nucleolus were not affected by the alcohol exposure. Analysis of Golgi-Cox-impregnated multipolar neurons showed that the alcohol exposure caused a reduction in area of the cell soma; a reduction in the number of dendritic branches; and a reduction in the complexity of the dendritic arbor relative to distance from the soma, based on concentric ring analysis. The results of this study demonstrate that gestational alcohol exposure can retard the maturation of the oculomotor nucleus.     

Alcohol exposure during development alters hypothalamic neurotransmitter concentrations

The effect of exposure to alcohol during a period roughly equivalent to the human third trimester on neurotransmitter content in the rat hypothalamus was examined. The alcohol exposure was accomplished via an artificial rearing procedure. The alcohol group was exposed to 5 g/kg/day of ethanol from postnatal day (PD) 4 to 10. There was an artificially reared control group not exposed to alcohol and a normally reared control group. Noradrenaline, dopamine, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were measured using high performance liquid chromatography with electrochemical detection in juvenile and adult rats. There were no effects in juvenile rats. In adult rats, alcohol exposure from PD 4 to 10 increased hypothalamic content of noradrenaline, dopamine, serotonin and 5-HIAA. While adult females had greater amounts of hypothalamic serotonin and 5-HIAA than adult males, there were no interactions of sex with alcohol exposure. These results suggest that hypothalamic function is seriously disrupted by alcohol exposure during development.