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J H Hannigan

Publications and source records attributed to J H Hannigan.

At least 19 recordsLinked to original sources
PubMed2000

Effects of prenatal alcohol exposure on the hippocampus: spatial behavior, electrophysiology, and neuroanatomy.

Prenatal exposure to alcohol can result in fetal alcohol syndrome (FAS), characterized by growth retardation, facial dysmorphologies, and a host of neurobehavioral impairments. Neurobehavioral effects in FAS, and in alcohol-related neurodevelopmental disorder, include poor learning and memory, attentional deficits, and motor dysfunction. Many of these behavioral deficits can be modeled in rodents. This paper reviews the literature suggesting that many fetal alcohol effects result, at least in part, from teratogenic effects of alcohol on the hippocampus. Neurobehavioral studies show that animals exposed prenatally to alcohol are impaired in many of the same spatial learning and memory tasks sensitive to hippocampal damage, including T-mazes, the Morris water maze, and the radial arm maze. Direct evidence for hippocampal involvement is provided by neuroanatomical studies of the hippocampus documenting reduced numbers of neurons, lower dendritic spine density on pyramidal neurons, and decreased morphological plasticity after environmental enrichment in rats exposed prenatally to alcohol. Electrophysiological studies also demonstrate changes in synaptic activity in in vitro hippocampal brain slices isolated from prenatal alcohol-exposed animals. Considered together, these observations demonstrate that prenatal exposure to alcohol can result in abnormal hippocampal development and function. Such studies provide a better understanding of neurological deficits associated with FAS in humans, and may also contribute to the development of strategies to ameliorate the effects of prenatal alcohol exposure on behavior.

Animals↗
PubMed2000

Alcohol in pregnancy and neonatal outcome.

Fetal alcohol syndrome (FAS) and other fetal alcohol effects in children are characterized by life-long compromises in growth, health, behaviour and cognitive ability. Most of the structural signs and many behavioural signs of FAS are evident at birth. This review describes the expression of fetal alcohol effects in neonates, including diagnostic criteria, alcohol withdrawal, pregnancy outcome, growth retardation, facial dysmorphology and behavioural outcomes.

Abortion, Spontaneous↗
PubMed2000

Effects of gestational alcohol exposure on the fatty acid composition of umbilical cord serum in humans.

This study examined the effects of maternal periconceptional alcohol intake on polyunsaturated fatty acid (PUFA) concentrations in human neonates. The area percentage of each fatty acid in cord blood serum from 12 infants born to control women (who consumed <2 mL absolute ethanol/d) was compared with that of 9 infants born to women whose periconceptional alcohol intake averaged > or = 30mL absolute ethanol/d. Periconceptional alcohol use was associated with a 30% increase in the proportion of docosahexaenoic acid (22:6n-3) in cord blood (3.0% of total lipid in control infants compared with 3.9% in alcohol-exposed infants; P < 0.01). The rise in the proportion of 22:6n-3 was responsible for increases in the ratio of n-3 to n-6 fatty acids and the ratio of long-chain n-3 to n-6 fatty acids (P < 0.055). Examination of the lipid-class fatty acid profile indicated that serum lipid alterations were localized to the cholesterol esters; 22:6n-3 in the cholesterol esters of alcohol-exposed infants increased 54% (P < 0.011) and arachidonic acid increased 55% (P < 0. 005). The relative fatty acyl composition of maternal serum showed a significant increase in 18:0 fatty acids in the alcohol-exposed group (25%, P < 0.005) but there were no changes in the other fatty acids. The increase in the proportion of 22:6n-3 was unexpected but is consistent with the hypothesis that this essential lipid may be conserved selectively. These results imply that the lifelong neurobehavioral and sensory dysfunction in fetal alcohol syndrome and other alcohol-related neurodevelopmental disorders may be due in part to PUFA dysregulation.

Adolescent↗
PubMed1999

Electrophysiology of hippocampal CA1 neurons after prenatal ethanol exposure.

In the present study, we examined the longitudinal effects of prenatal ethanol exposure on the electrophysiological characteristics of CA1 neurons in hippocampal slices. Hippocampal slices were obtained from young (25-32-day old) and adult (63-77-day old) male offspring of rats given one of four treatments during gestation. Three groups of pregnant rats were orally intubated with 0, 4, or 6 g/kg ethanol on gestational days 8-20. Caloric intake for the 0- (nutritional control) and 4-g/kg groups was yoked to that of the 6 g/kg group. A fourth group (untreated control) was not intubated, and was given ad lib access to food. Long-term potentiation and paired-pulse inhibition were unaffected by prenatal ethanol exposure in young and adult rats; however, slices taken from the young 6 g/kg ethanol group displayed a significantly lower maximal CA1 population spike amplitude evoked by Schaffer collateral stimulation as compared to young controls. This difference was not observed in adult animals. These data suggest that some aspects of hippocampal physiology are negatively affected in young rats as a result of prenatal ethanol exposure, but this effect reverses as the animal matures.

Aging↗
PubMed1999

Prenatal ethanol reduces the activity of adult midbrain dopamine neurons.

BACKGROUND: Prenatal ethanol exposure has been demonstrated to reduce dopamine (DA) neurotransmission in the forebrain area, which could be contributed by altered electrical activity in midbrain DA neurons. This hypothesis was tested in the present study. METHODS: The effects of prenatal ethanol exposure on the spontaneous activity of DA neurons in the substantia nigra and ventral tegmental area were investigated with extracellular single-unit recording techniques in adult male rats. Pregnant rats were administered single daily doses of 0, 3, or 5 g/kg ethanol via intragastric intubation from gestation day 8 through 20. An additional control group did not receive the intubation procedure. RESULTS: Prenatal ethanol treatment significantly reduced the number of spontaneously active DA neurons in the substantia nigra and ventral tegmental area in 3- to 5-month-old male offspring. The firing rate and firing pattern of the remaining spontaneously active DA neurons were not altered. There were no differences in the spontaneous activity of DA neurons between the nonintubated and 0 g/kg control groups, indicating possible intubation-induced stress did not influence the activity of DA neurons in adult offspring. Similar prenatal ethanol effects were also determined from older animals (14-16 months old), suggesting that the reduction in the spontaneous activity of DA neurons is a persistent phenomenon in adulthood after prenatal ethanol exposure. Furthermore, the reduction in the number of spontaneously active DA neurons was not the result of a loss in DA neurons per se, as revealed by the results of tyrosine hydroxylase immunohistochemistry. The prenatal ethanol exposure-induced reduction in DA neuronal activity may result from depolarization inactivation, because systemically administered apomorphine (20 microg) increased the spontaneous activity of DA neurons. CONCLUSIONS: Prenatal ethanol exposure induced a long-lasting reduction in the activity of midbrain DA neurons in adult animals. The effect was not the result of cell loss but possible changes in the electrical properties of DA neurons. The decreased electrical activity in midbrain DA neurons could contribute to the prenatal ethanol exposure-induced reduction in DA content and metabolites observed in previous studies and the attention/hyperactivity problems reported in children with fetal alcohol effects/fetal alcohol syndrome.

Animals↗
PubMed1996

What research with animals is telling us about alcohol-related neurodevelopmental disorder.

The substantial advances in understanding fetal alcohol syndrome over the past 20 years were made in large part because of research with animals. This review illustrates recent progress in animal research by focusing primarily on the central nervous system effects of prenatal alcohol exposure. Current findings suggest further progress in understanding consequences, risk factors, mechanisms, prevention and treatment will depend on continued research with animals.

Animals↗
PubMed1995

Reversal of alcohol's effects on neurite extension and on neuronal GAP43/B50, N-myc, and c-myc protein levels by retinoic acid.

Alcohol teratogenesis may be due in part to inhibition of neuronal differentiation by ethanol. We showed previously that alcohol decreased neuronal differentiation (neurite extension) and increased N-myc and c-myc neuronal protein levels. Since Growth-Associated Protein 43 (GAP43/B50) levels must increase for neurons to differentiate, alcohol may decrease GAP43/B50. Alcohol dose-dependently (0-0.5%) decreased GAP43/B50 protein levels by up to 92% in immature LA-N-5 cells. Five nM retinoic acid alone induced differentiation and increased GAP43/B50 levels to 230% of control. These retinoic acid-induced increases in GAP43/B50 and neurite outgrowth, and decreases in N-myc and c-myc, were reversed dose-dependently by alcohol (0-0.5%). Conversely, the adverse effects of 0.25% alcohol on neurite extension, GAP43/B50, N-myc, and c-myc were prevented by 15 and 45 nM retinoic acid. These results suggest that inhibition of neuronal differentiation by alcohol and prevention of such effects by retinoic acid are related to changes in GAP43/B50, N-myc and c-myc.

Cell Differentiation↗
PubMed1995

Independent associations among maternal alcohol consumption and infant thyroxine levels and pregnancy outcome.

Studies with animal models of alcohol-related birth defects (ARBDs) suggest that reductions in circulating thyroid hormones, including thyroxine (T4), may be a persistent postnatal effect of fetal alcohol exposure. The few clinical reports of children with fetal alcohol syndrome (FAS) that address thyroid system function generally reported that FAS children have thyroid hormone levels within normal limits. For the current study, data bases from the Fetal Alcohol Research Center and the Michigan Department of Public Health Newborn Screening Program were assessed to correlate measures of maternal drug use during pregnancy and infant outcome (gestational age at birth, birthweight, "fetal growth"), with infant whole-blood T4 levels. Multiple regression analyses accounted for demographic factors, infant age at testing, and variation in the T4 assay. As expected, alcohol intake and smoking each had a substantial negative impact on birthweight, gestational age at birth, and fetal growth, assessed as birthweight corrected for gestational age. Infant T4 levels were positively related to birthweight and gestational age and were more strongly related to fetal growth. Infant T4 levels were not influenced significantly by either maternal smoking or alcohol consumption. Smoking- and alcohol-related reductions in birthweight, gestational age, or fetal growth were not associated significantly with variations in infant T4. Interesting questions remain regarding species differences and the influences of maternal alcohol consumption on T4 metabolism as a mechanism for ARBDs. However, the current data do not support the hypothesis that maternal alcohol consumption, or smoking, during pregnancy leads to compromised thyroid system function in newborn humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Effects of prenatal exposure to alcohol plus caffeine in rats: pregnancy outcome and early offspring development.

The factors determining susceptibility to fetal alcohol syndrome (FAS) are not fully understood. We used an animal model of alcohol-related birth defects to assess the coteratogenic potential of caffeine as a risk factor in FAS. Rats were exposed prenatally to alcohol (approximately 15 g/kg/day) with or without caffeine (approximately 84 mg/kg/day) from gestation days 6 through 20 via liquid diet. All control groups were pair-fed to the alcohol-exposed groups. In addition, some controls had free access to lab chow and water. Prenatal exposure to alcohol or caffeine reduced both maternal weight gain during pregnancy and birth-weight of offspring. The combination of alcohol plus caffeine produced an additive effect in reducing birthweight and synergistic effects in increasing postnatal offspring mortality. Prenatal alcohol exposure had a significant negative impact on several developmental indices, including grip strength and negative geotaxis. Prenatal caffeine exposure did not affect maturational measures and did reduce offspring serum levels of the zinc-dependent enzyme alkaline phosphatase. This study in rats demonstrated that caffeine can exacerbate some of the effects of alcohol on prenatal development, specifically reduced birthweight, litter size, and postnatal survival, but that caffeine does not appear to alter prenatal alcohol-induced delays in early postnatal maturation of survivors. The relative impact of intralitter birthweight rank on developmental outcome was also assessed.

Animals↗
PubMed1995

'J-shaped' relationship between drinking during pregnancy and birth weight: reanalysis of prospective epidemiological data.

Worldwide epidemiological studies on the effects of drinking during pregnancy on birth weight and prematurity were surveyed. Far more studies have reported no significant effects on birth weight than have reported significant decreases. Statistical analyses of the means from the prospective studies in this area indicated that both maternal smoking and alcohol consumption during gestation are associated with a significant decrease in birth weight. The effect of smoking is three times greater than the effect of alcohol. When the data were stratified by smoking status, maternal alcohol consumption did not have a significant effect on birth weight for non-smokers, but among smokers there was a significant linear trend with a threshold for decreased birth weight at about an average of two drinks per day. There was also a significant pattern of increased birth weight associated with low levels of alcohol consumption, suggesting an inverted 'J-shaped' function between drinking during pregnancy and birth weight.

Alcohol Drinking↗
PubMed1995

The effects of chronic amphetamine treatment on prenatal ethanol-induced changes in dopamine receptor function: electrophysiological findings.

The sensitivity of dopamine (DA) receptors in the mesoaccumbens DA system was investigated with extracellular recording and microiontophoresis techniques in adult rats that received prenatal ethanol exposure and chronic postnatal amphetamine treatment. Pregnant rats were fed with a liquid diet containing 0 or 35% ethanol-derived calories from gestation day 6 to 20. An ad libitum group received laboratory chow and water. Offspring were injected with amphetamine (2 mg/kg/day s.c.) or saline from postnatal day 22 to 10- to 12-months of age. Electrophysiological recording procedures were performed 16 to 24 hr after the last amphetamine injection. A supersensitivity of somatodendritic DA autoreceptors in the ventral tegmental area was observed in animals exposed prenatally to ethanol. This prenatal ethanol exposure-induced supersensitivity was not observed after postnatal amphetamine treatment. In control animals, postnatal amphetamine treatment did not affect the sensitivity of somatodendritic DA autoreceptors. The sensitivity of D-1 DA receptors in the nucleus accumbens was reduced by prenatal ethanol exposure. Postnatal amphetamine treatment reduced D-1 DA receptor sensitivity in control animals, but not in animals exposed prenatally to ethanol. Neither prenatal ethanol treatment nor postnatal amphetamine treatment altered the sensitivity of D-2 DA receptors in the nucleus accumbens. There were no differences between the ad libitum and 0% ethanol-derived calorie groups, indicating undernutrition did not affect DA receptor function. These results show that prenatal ethanol exposure altered DA receptor function in the mesoaccumbens DA system in adult animals. Furthermore, postnatal amphetamine treatment was able to eliminate the supersensitivity of somatodendritic DA autoreceptors in prenatal ethanol-exposed animals.

Amphetamines↗
PubMed1994

The immobility response in the forced swim test: paradoxical effect of imipramine.

Rats immersed in a modified version of the forced swim test in which they are unable to touch the bottom of the cylinder with their feet while keeping their noses above water, initially paddle vigorously but eventually become relatively immobile. In the present study, we show that chronic treatment with imipramine and alprazolam increases rather than decreases the immobility response of rats in this test, whereas chronic treatment with propranolol is less effective. The results of this study indicate that the interpretation of the immobility response as 'behavioral despair', which is based on the response to the antidepressant drugs such as imipramine, needs to be reevaluated.

Alprazolam↗
PubMed1992

Effects of chronic forced swimming and exposure to alarm substance: physiological and behavioral consequences.

Rats tested for 7 consecutive days in the forced swim test in fresh water were more immobile than those tested in soiled water on all days. Animals in both water conditions increased their immobility times slightly over days, but animals tested in soiled water, which presumably contained an alarm substance, never attained the immobility times of those tested in fresh water. When animals were switched between fresh and soiled water, they behaved exactly like animals in the water condition to which they were switched. Prior inescapable forced swimming in either water condition affected subsequent escape in a Morris water maze, but more so for animals tested only in fresh water. A second study corroborated the escape results. Serum corticosterone and relative adrenal weights were increased as a result of forced swimming but escape performance differences could not be attributed to differences in the stress-provoking consequences of the two water conditions.

Animals↗
PubMed1990

Lower serum thyroxine levels in rats following prenatal exposure to ethanol.

Fetal alcohol syndrome (FAS) is noted for poor growth, developmental delays, and mental retardation. In animals, prenatal alcohol exposure alters anatomical, physiological, and neurochemical maturation and produces behavioral changes similar to those in children. Since thyroid hormones are critical trophic factors for normal somatic and neural maturation, and since fetal thyroid hormones are profoundly affected by acute maternal ethanol administration, we hypothesized that postnatal effects of prenatal alcohol exposure may be related to abnormal thyroid hormone development. We report here that young rats exposed to alcohol in utero have significantly lower serum total thyroxine (T4) concentrations than normal and pair-fed control rats. The results suggest prenatal ethanol exposure may compromise thyroid development in ways not attributable to undernutrition or developmental delays alone. Lowered total T4 levels may be a teratogenic outcome of prenatal alcohol exposure, which could contribute to impaired growth, altered neural organization, and behavioral dysfunction.

Alcohol Drinking↗
PubMed1990

Caudate neurons respond to excitatory and inhibitory amino acids in early postnatal periods in the cat.

This study was designed to determine whether caudate neurons would respond to microphoretic application of glutamate and gamma-aminobutyric acid (GABA) in early postnatal periods in the cat. Extracellular recordings were performed in 175 neurons in developing kittens and 114 neurons in adult cats. At the earliest ages tested (1-10 days), caudate cells were excited by microphoretic application of glutamate and were inhibited by application of GABA. The results also indicated that caudate units have lower response thresholds to application of glutamate and GABA in early postnatal periods than in later periods. Since previous findings indicated that synaptically mediated inhibitory potentials develop during later postnatal periods in the cat, the present findings suggest that receptors for GABA may be capable of functioning before presynaptic endings make operational contacts.

Action Potentials↗
PubMed1989

Cholinergic maturation and SCH 23390-induced catalepsy in the male rat pup.

The cataleptogenic effects of the selective dopamine D1 receptor antagonist, SCH 23390, increased between 13 and 17 days of age in male pups. Seventeen- and 21-day-old pups showed equivalent catalepsy. Scopolamine blocked SCH 23390-induced catalepsy in 21-day-old pups but had little effect in 13-day-old pups. The development and cholinergic sensitivity of SCH 23390-induced catalepsy are similar to those seen after D2 or mixed D1/D2 receptor blockade. Cholinergic maturation appears to be an important component in the development of adult-like catalepsy, and the nature of a D1-acetylcholine interaction mediating catalepsy remains to be determined.

Aging↗
PubMed1987

Altered grooming responses to stress in rats exposed prenatally to ethanol.

The effects of prenatal alcohol exposure on grooming, locomotion, and rearing in response to stress were examined in adult rats whose mothers consumed a liquid diet containing 35% ethanol-derived calories (EDC). Offspring of both pair-fed 0% EDC mothers and ad libitum chow-fed mothers were included as controls. In Experiment 1, females groomed more than males following placement into a novel test chamber, but no differences due to prenatal treatment were observed. Ethanol-exposed animals groomed more than controls following the stress of a forced 1-min swim (Experiment 2), but when rats tested in Experiment 1 were observed again after forced swim stress (Experiment 3), no differences due to prenatal treatment or sex were observed. Experiment 4 examined the effects of pretreatment with 1 mg/kg naloxone on novelty-induced grooming and as in Experiment 1 prenatal treatment did not affect grooming responses. Females again groomed significantly more than males and naloxone reduced grooming equally for all groups. The results suggest that novelty-induced grooming is a sex-influenced behavior, with females grooming more than males, and that animals exposed prenatally to alcohol and tested as adults may have altered responses to certain stressors (i.e., forced swim) under specific conditions. The altered grooming response of alcohol-exposed rats to swim stress can be eliminated by preexposing them to novelty stress.

Animals↗