Implicit strategy affects learning in children with heavy prenatal alcohol exposure

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.     

Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure

BACKGROUND: Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. METHODS: The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. RESULTS: Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. CONCLUSIONS: These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor delays in children with FAS may be related to specific neurobehavioral deficits that affect fine motor skills. The findings support the concept of an FASD continuum in some areas of motor development.     

Comparison of verbal learning and memory in children with heavy prenatal alcohol exposure or attention-deficit/hyperactivity disorder

Background: Children with fetal alcohol spectrum disorders (FASD) have deficits in verbal learning and recall. However, the specificity of these deficits has not been adequately tested. In the current study, verbal learning and memory performance of children with heavy prenatal alcohol exposure was compared to children with attention‐deficit/hyperactivity disorder (ADHD), a disorder commonly seen in alcohol‐exposed children. Methods: Performance on the California Verbal Learning Test—Children’s Version (CVLT‐C) was examined in 3 groups of children (N = 22/group): (i) heavy prenatal alcohol exposure and ADHD (ALC), (ii) nonexposed with ADHD (ADHD), and (iii) nonexposed typically developing (CON). Groups were matched on age, sex, race, ethnicity, handedness, and socioeconomic status (SES). Results: Group differences were noted on learning trials (CON > ADHD > ALC). On the delayed recall trial, CON children performed better than both clinical groups, who did not differ from each other. Children in the ALC group demonstrated poorer recognition than children in the CON and ADHD groups, who did not differ from each other. Marginally significant group differences were noted on retention of previously learned material. Post hoc analyses indicated that ADHD children showed worse retention relative to the CON group, whereas retention in the ALC children remained intact. Conclusions: These data suggest that children with heavy prenatal alcohol exposure and nonexposed children with ADHD show differential patterns of deficit on the CVLT‐C. Performance of alcohol‐exposed children reflects inefficient encoding of verbal material, whereas performance of the ADHD group may be better characterized by a deficit in retrieval of learned material. Differences noted between clinical groups add to a growing neurobehavioral profile of FASD that may aid in differential diagnosis.     

A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: profiles, mechanisms, and interventions

Background: Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. Methods: The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). Results: Social deficits are found in alcohol‐exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. Conclusions: Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation.     

The effects of maternal binge drinking during pregnancy on neural correlates of response inhibition and memory in childhood

Background: Although an extensive literature has documented a broad range of cognitive performance deficits in children with prenatal alcohol exposure, little is known about how the neurophysiological processes underlying these deficits may be affected. Event‐related potentials (ERPs), which reflect task‐specific changes in brain electrical activity, provide a method for examining multiple constituents of cognitive processing at the neural level. Methods: We recorded ERPs in 217 children from Inuit communities in Arctic Quebec (M age = 11.3 years) during 2 different tasks—Go/No‐go response inhibition and continuous recognition memory. Children were classified as either alcohol‐exposed (ALC) or controls (CON) depending on whether the mother reported binge drinking during pregnancy. Results: Both groups performed comparably in terms of accuracy and reaction time on the tasks, and both tasks elicited the expected effects on ERPs when responses were compared across conditions. However, the ALC group showed slower P2 latencies on Go/No‐go, suggesting an altered neurophysiological response associated with initial visual processing of the stimuli. On the memory task, the ALC group showed reduced FN400 amplitude to New items, known as the familiarity effect, and reduced amplitude for the late positive component, possibly reflecting impairment in memory retrieval. Conclusions: These findings show that, even in tasks in which alcohol‐exposed children exhibit behavioral performance that is comparable to controls, fetal alcohol exposure is associated with altered neurophysiological processing of response inhibition and recognition memory. The data suggest that fetal alcohol exposure is associated with reduced efficiency in the initial extracting of the meaning of a stimulus, reduced allocation of attention to the task, and poorer conscious, explicit recognition memory processing.     

Acquisition and retention of verbal and nonverbal information in children with heavy prenatal alcohol exposure

BACKGROUND: Memory deficits are reported commonly in children with fetal alcohol syndrome. However, little is known about nonverbal memory performance in this population. METHODS: The current study examined learning and memory abilities in alcohol-exposed children and nonexposed controls. Multiple verbal and nonverbal measures were used that incorporated repeated learning trials and delayed recall trials. The alcohol-exposed group included children with heavy prenatal alcohol exposure with and without fetal alcohol syndrome. Children ranged in age from 8 to 16 years, and groups were matched on age, sex, ethnicity, and socioeconomic status. RESULTS: Children with heavy prenatal alcohol exposure displayed deficits in learning and recall of verbal and nonverbal information across all measures. On learning trials, they recalled fewer words and displayed a lower rate of acquisition. However, when we analyzed delayed verbal recall data after controlling for initial verbal learning, group differences were not apparent. The same pattern did not occur for nonverbal information; children with prenatal alcohol exposure recalled less on delayed recall even when we accounted for initial learning. CONCLUSIONS: These data are consistent with previous studies that indicate immediate memory deficits but suggest that, at least for verbal information, delayed recall deficits in this population are better accounted for by deficits in initial learning. Importantly, a different pattern of results was demonstrated for verbal versus nonverbal information, which suggests the need for additional research in this area.     

Markers of oxidative stress and systemic vasoconstriction in pregnant women drinking > or =48 g of alcohol per day

Background: The precise pathway by which alcohol causes the characteristic features of fetal alcohol spectrum disorders is unknown. Proposed mechanisms for fetal injury from maternal alcohol use include cellular damage from oxidative stress and impaired fetal oxygenation related to maternal systemic vasoconstriction. Our objective was to compare the levels of urinary markers of oxidative stress and systemic vasoconstriction between women consuming large amounts of alcohol during pregnancy and women who did not drink alcohol during pregnancy. Methods: Pregnant women consuming ≥48 g alcohol per day (n = 29) on average and pregnant women who abstained from alcohol use (n = 39) were identified using detailed interviews and home visits. Random maternal urine specimens were collected. Urinary levels of the oxidative stress marker, 8‐isoprostane F2α, and of the vasoactive prostaglandin metabolites, 2,3‐dinor‐6‐keto‐prostaglandin F1α (a vasodilator) and 11‐dehydro‐thromboxane B2 (a vasoconstrictor), were measured using mass spectrometric methods. All analyte levels were corrected for urinary creatinine. Results: In crude analyses, there was no significant difference in 8‐isoprostane F2α between pregnant drinkers and nondrinkers (2.16 vs. 2.08 ng/mg creatinine, respectively, p = 0.87). There were no significant differences between the drinking and nondrinking groups in levels of 2,3‐dinor‐6‐keto‐prostaglandin F1α (1.03 vs. 1.17 ng/mg creatinine, repectively, p = 0.50), 11‐dehydro‐thromboxane B2 (0.72 vs. 0.59 ng/mg creatinine, respectively, p = 0.21), or the ratio of vasodilatory metabolite to vasoconstrictive metabolite (1.73 vs. 2.72, respectively, p = 0.14). Adjusting for maternal age, marital status, smoking, and gestational age at sampling did not substantially alter the results. Conclusion: Our results show no difference in levels of urinary eicosanoid markers of oxidative stress and systemic vasoconstriction between pregnant women who drink heavily and pregnant women who abstain. These findings speak against a role for maternal oxidative stress or systemic vasoconstriction in the pathogenesis of alcohol damage to the fetus.     

Persistent impairment of hippocampal neurogenesis in young adult rats following early postnatal alcohol exposure

Background: Prenatal alcohol exposure can cause damage to the developing fetus with outcomes including growth deficiency, facial dysmorphology, brain damage, and cognitive and behavioral deficits. Smaller brains in children with FASD have been linked both with reduced cell proliferation in the developing CNS and with apoptotic cell loss of postmitotic neurons. Prenatal alcohol exposure in rodents during the period of brain development comparable to that of the first and second trimesters of human pregnancy persistently alters adult neurogenesis. Long‐term effects of alcohol exposure during the third trimester equivalent, which occurs postnatally in the rat, on adult neurogenesis have not been previously reported. The goal of this study was to examine the effect of postnatal binge‐like alcohol exposure on cell proliferation and neurogenesis in hippocampal dentate gyrus during adolescence and young adulthood. Methods: Male Long‐Evans rat pups were assigned to 3 groups: alcohol‐exposed (AE), sham‐intubated (SI) or suckle control (SC). AE pups received ethanol in a milk formula in a binge manner (2 feedings, 2 hours apart, total dose 5.25 g/kg/day) on postnatal days (PD) 4–9. BrdU was injected every other day on PD30–50. Animals were perfused either on PD50 to examine cytogenesis and neurogenesis in hippocampal dentate gyrus at the end of BrdU injections or on PD80 to evaluate new cell survival. Dorsal hippocampal sections were immunostained for BrdU, a marker for proliferating cells, Ki67, endogenous marker of proliferation, and NeuN, a marker for mature neurons. Results: Binge‐like alcohol exposure on PD4–9 significantly reduced the number of mature neurons in adult hippocampal dentate gyrus (DG) both on PD50 and PD80, without altering cumulative cytogenesis on PD50. In addition, the number of new neurons, that were generated between PD30 and 50, was further reduced after 30 days of survival in all 3 groups (SC, SI, and AE). Conclusions: These observations suggest that early postnatal binge alcohol exposure results in long‐term deficits of adult hippocampal neurogenesis, providing a potential basis for the deficits of hippocampus‐dependent behaviors reported for this model.     

Effects of dose and period of neonatal alcohol exposure on the context preexposure facilitation effect

Background: Alcohol exposure in the rat on postnatal days (PD) 4 to 9 is known to partially damage the hippocampus and to impair hippocampus‐dependent behavioral tasks. We previously reported that PD4 to 9 alcohol exposure eliminated the context preexposure facilitation effect (CPFE) in juvenile rats, a hippocampus‐dependent variant of contextual fear conditioning. In the CPFE, context exposure and immediate shock occur on successive occasions and this produces conditioned freezing relative to a control group that is not preexposed to the training context. Here, we extend our earlier findings by examining the effects of neonatal alcohol administered at multiple doses or over different neonatal exposure periods. Method: Rat pups (male and female) were exposed to a single binge dose of alcohol at one of 3 doses (2.75, 4.00, or 5.25 g/kg/d) over PD4 to 9 (Experiment 1) or to 5.25 g over PD4 to 6 or PD7 to 9 (Experiment 2). Sham‐intubated (SI) and undisturbed (UD) rats served as controls. On PD31, rats were preexposed to either the training context (Pre) or an alternate context (No‐Pre). On PD32, rats received an immediate unsignaled footshock (1.5 mA, 2 seconds) in the training context. Finally, on PD33, all rats were returned to the training context and tested for contextual freezing over a 5‐minute period. Results: Undisturbed‐ and SI‐Pre rats showed the CPFE, i.e., context preexposure facilitated contextual conditioning, relative to their No‐Pre counterparts. The immediate shock deficit was present in all No‐Pre groups, regardless of previous alcohol exposure. In Experiment 1, blood alcohol level was negatively correlated with contextual freezing. Group 2.75 g‐Pre did not differ from controls. Group 4.00 g‐Pre froze significantly less than Groups UD‐ and SI‐Pre but more than Group 5.25‐Pre, which showed the immediate shock deficit. In Experiment 2, alcohol exposure limited to PD7 to 9, but not PD4 to 6, disrupted the CPFE. Conclusions: This is the first demonstration of dose‐related impairment on a hippocampus‐dependent task produced by neonatal alcohol exposure in the rat. Exposure period effects support previous studies of alcohol and spatial learning. The CPFE is a more sensitive behavioral task that can be used to elucidate developmental alcohol‐induced deficits over a range of alcohol doses that are more relevant to human exposure levels.     

An Event‐Related Potential Study of Response Inhibition in ADHD With and Without Prenatal Alcohol Exposure

Background: The attention and cognitive problems seen in individuals with a history of prenatal alcohol exposure often resemble those associated with attention deficit hyperactivity disorder (ADHD), but few studies have directly assessed the unique influence of each on neurobehavioral outcomes. Methods: We recorded event‐related potentials (ERPs) during a Go/No‐go response inhibition task in young adults with prospectively obtained histories of prenatal alcohol exposure and childhood ADHD. Results: Regardless of prenatal alcohol exposure, participants with childhood ADHD were less accurate at inhibiting responses. However, only the ADHD group without prenatal alcohol exposure showed a markedly diminished P3 difference between No‐go and Go, which may reflect a more effortful strategy related to inhibitory control at the neural processing level. Conclusion: This finding supports a growing body of evidence suggesting that the manifestation of idiopathic ADHD symptoms may stem from a neurophysiologic process that is different from the ADHD symptomatology associated with prenatal alcohol exposure. Individuals who have been prenatally exposed to alcohol and present with ADHD symptomatology may represent a unique endophenotype of the disorder, which may require different treatment approaches from those found to be effective with idiopathic ADHD.     

Web-based assessment and brief intervention for alcohol use in women of childbearing potential: a report of the primary findings

Background: There is a need for more effective assessment and primary prevention programs aimed at accurately measuring and reducing alcohol consumption among women before conception in underserved, high‐risk populations. Health information technology may serve this purpose; however, the effectiveness of such tools within this population is not known. Methods: We conducted a small‐scale randomized controlled trial to test the effectiveness of an adapted web‐based alcohol assessment and intervention tool among low‐income, nonpregnant women of reproductive age who were receiving Women Infant and Children (WIC) services in San Diego County and who reported currently drinking at a moderate risk level. A total of 150 risky drinking participants completed a web‐based assessment and were randomly assigned to either receive a personalized feedback intervention or general health information about alcohol consumption and fetal alcohol syndrome. Follow‐up assessments on reported alcohol consumption were conducted via telephone at 1‐ and 2‐months postbaseline. Participants ranged in age from 18 to 44 and were predominately Hispanic/Latina (44%). Results: At baseline, all respondents reported consuming ≥3 standard drinks on ≥1 occasion in the previous month. Outcome data were available for 131 participants. The main outcome measure was reduction in the number of risky drinking occasions, which did not differ significantly between treatment conditions (odds ratio 1.200, 95% CI 0.567 to 2.539, p = 0.634). Over 70% of the participants, however, reported a reduction in risky drinking occasions regardless of treatment condition (control 43/63, 68%; experimental 49/68, 72%). Conclusions: The results of this study demonstrate that web‐based assessment of alcohol consumption among low‐income women of reproductive age, as represented by WIC clients, is feasible and acceptable. The findings also suggest that detailed and interactive assessments of alcohol consumption may be sufficient for the reduction of risky drinking within this population without personalized feedback.     

Fetal alcohol exposure alters GAP-43 phosphorylation and protein kinase C responses to contextual fear conditioning in the hippocampus of adult rat offspring

Abstract : Background: The growth‐ and plasticity‐associated protein GAP‐43 plays a significant role in the establishment and remodeling of neuronal connections. We have previously shown that GAP‐43 levels, protein kinase C (PKC) activity, and GAP‐43 phosphorylation increase during contextual fear conditioning and that fetal alcohol exposure (FAE) decreases PKC activity and GAP‐43 phosphorylation in the hippocampus of adult offspring. Drawing on these observations, we hypothesized that FAE manifests its cognitive impairment by disrupting PKC activation and membrane translocation, thereby decreasing GAP‐43 phosphorylation and function. Methods: Three groups of pregnant rat dams (FAE and two control diet groups) were placed on different diet regimens. Offspring from each of these groups were placed into each of four test groups, a contextual fear conditioned (CFC) group, a naïve unhandled group, and two nonlearning stress control groups. Hippocampi were dissected, homogenized, and used to prepare a cytosolic and a membrane fraction. These fractions were probed for total GAP‐43, PKC‐phosphorylated GAP‐43, and several PKC subtypes. PKC activity also was measured in total homogenates. Results: Compared with both control diet groups, FAE animals showed a deficit in the activation of PKC in the hippocampus at 24 hr but not at 1.5 hr after CFC. Likewise, we found that the amount of GAP‐43 and its phosphorylation were decreased 24 hr after CFC in FAE rats but not at early times after training. Analysis of the translocation of various PKC isoforms revealed that FAE animals had decreased levels of membrane‐bound PKC β₂ and PKC ε 24 hr after CFC. Conclusions: Considering the role of PKC activation and GAP‐43 phosphorylation in synaptic plasticity, our results suggest that deficient translocation of PKC β₂ and PKC ε in the hippocampus may mediate the electrophysiological and behavioral deficits observed in fetal alcohol exposed animals.     

Fetal alcohol exposure and temporal vulnerability: regional differences in cell loss as a function of the timing of binge-like alcohol exposure during brain development

This study was conducted to determine the temporal and regional vulnerability of the brain as a function of exposure to alcohol during brain development. Our goal was to manipulate the timing of alcohol exposure and assess the relative risk of cell loss in two different brain regions. Groups of timed pregnant Sprague-Dawley rats received binge-like alcohol exposure during either the first 10 days (first-trimester equivalent) or second 10 days of gestation (second-trimester equivalent), or the combination of first- and second-trimester equivalents for prenatal treatments. Offspring from some of the animals exposed to alcohol during the combined first- and second-trimester equivalent were reared artificially from postnatal days (P) 4 through 9 (part of the third-trimester equivalent) and also received binge-like alcohol during this period, producing animals that were exposed to alcohol during all three trimesters equivalent. Offspring from untreated dams were also reared artificially and received alcohol from only P4-9, thus creating animals that were exposed to alcohol only during part of the third-trimester equivalent. All pups were perfused on P10. Appropriate controls (nutritional and normally reared) were matched to every alcohol treatment combination. Peak blood alcohol concentrations were not different among the treatment groups for a given sampling time. Total cell numbers in the cerebellum (Purkinje and granule cells) and the olfactory bulb (mitral and granule cells) were estimated by the unbiased stereological technique, the optical disector. In terms of temporal vulnerability, alcohol exposure during the equivalent of all three trimesters resulted in a greater reduction in cerebellar Purkinje cell numbers compared with exposure to alcohol during the third-trimester equivalent, whereas both groups had a significant reduction in cell number compared with all other timing groups. Cerebellar granule cell number was reduced after alcohol exposure during all three trimesters equivalent, compared with all other timing groups. Alcohol exposure during the third-trimester equivalent resulted in a decrement in the number of olfactory bulb mitral cell numbers compared with all other groups, but there were no differences among the timing groups in numbers of olfactory bulb granule cells. When the cell loss in the two regions was compared within each alcohol treatment group to determine the relative regional vulnerability, the primary salient finding was that cerebellar Purkinje cells were more vulnerable to alcohol-induced loss subsequent to exposure during all three trimesters equivalent. No other regional differences were detected. These results extend earlier findings by showing that alcohol exposure during different periods of brain development results in regional differences in cell loss as a function of the timing of alcohol exposure during brain development and illustrate the variability of alcohol-induced neuronal loss.     

Prenatal ethanol exposure reduces mGluR5 receptor number and function in the dentate gyrus of adult offspring

BACKGROUND: Previous studies in our laboratory indicated that metabotropic glutamate receptor (mGluR)-stimulated phosphoinositide hydrolysis is markedly reduced in the hippocampal formation of adult rat offspring whose mothers drank moderate amounts of ethanol during pregnancy. In the present study, we extended these observations by measuring the impact of prenatal ethanol exposure on proteins associated with the mGluR5 receptor-effector system along with two mGluR5 agonist-mediated responses in dentate gyrus of adult offspring. METHODS: Sprague-Dawley rat dams consumed one of three diets throughout gestation: (1) a BioServ liquid diet that contained 5% ethanol (v/v), (2) pair-fed an isocalorically equivalent amount of 0% ethanol liquid diet, or (3) lab chow ad libitum. Microdissected slices of dentate gyrus were prepared from adult female offspring from each diet group and used for (1) Western blot analyses of mGluR5, the G-proteins Galphaq and Galpha11, and phospholipase C-beta1; (2) 2-chloro-5-hydroxyphenylglycine (CHPG)-stimulated growth associated protein 43 (GAP-43) phosphorylation; or (3) CHPG potentiation of electrically evoked [H]-D-aspartate (D-ASP) release from dentate gyrus slices. RESULTS: In tissue prepared from untreated control rats, CHPG produced a dose-dependent increase in phosphate incorporation into GAP-43, with maximal agonist stimulation occurring at 20 microM of CHPG. CHPG produced a quantitatively similar dose-dependent increase in the potentiation of electrically evoked D-ASP release from dentate gyrus slices from untreated controls. Fetal ethanol exposure reduced the amount of dentate gyrus mGluR5 receptor protein by 36% compared with the diet control groups. There were no significant differences between diet groups in the two G-proteins or phospholipase C-beta1 protein. Fetal ethanol exposure reduced CHPG-stimulated GAP-43 phosphorylation to approximately one half the amount of CHPG stimulation observed in the control diet groups. Prenatal ethanol exposure also reduced CHPG potentiation of D-ASP release to a similar degree compared with control. CONCLUSIONS: These results indicate that prenatal exposure to moderate quantities of ethanol reduces mGluR5 expression in the dentate gyrus of adult offspring. Although the subcellular site(s) for reduced mGluR5 expression cannot be discerned from Western blot data, the quantitatively similar effects of prenatal ethanol exposure on mGluR5 agonist stimulation of presynaptically localized GAP-43 phosphorylation and CHPG potentiation of evoked D-ASP release suggest that the presynaptic nerve terminal is one site where prenatal ethanol exposure has reduced mGluR5 receptor number and function. Furthermore, these data implicate these neurochemical alterations as one factor contributing to the hippocampal synaptic plasticity and behavioral deficits that we have observed previously in prenatal ethanol-exposed offspring.