Edward Reyes

The effects of prenatal alcohol exposure on radial arm maze performance in adult rats.

The hippocampal formation is sensitive to the in utero exposure to ethanol. It is one brain area thought to play an important role in spatial memory. We examined radial arm maze performance in rats exposed to ethanol prenatally. Pregnant rats were placed into the following treatment groups: LC, 17% EDC (ethanol-derived calories), 35% EDC, PF 35% or PF 17%. The LC group was fed lab chow and water ad lib, the 17% EDC and 35% EDC groups were fed a liquid diet containing either 3.3% or 6.7% v/v ethanol, respectively. Pair-fed controls were fed the same volume of an isocaloric diet as was consumed by their respective ethanol-treated groups. At birth, litters were culled to six and cross fostered to untreated surrogate mothers. Testing was initiated at 60 days of age and continued until the test criterion was satisfied. One-half of the rats in the 35% EDC group did not reach criterion. The remainder of the 35% EDC group and the 17% EDC rats attained criterion but required twice as many trials as their respective pair-fed controls. These results suggest that in utero administration of ethanol affects spatial memory capacity in rat, an observation consistent with other deficits seen in hippocampus of rats prenatally exposed to ethanol.

Protective effects of the flavonoid mixture, silymarin, on fetal rat brain and liver

We investigated the possibility that the flavonoid mixture, silymarin (SY), administered as the compound Silymarin Phytosome (PHYTO), could protect the fetus from maternally ingested EtOH. Seventy-six female rats were randomly assigned to one of seven groups: pair-fed control; chow fed control; EtOH; and four groups receiving EtOH and PHYTO in varying dosages. All groups except the chow-fed control were maintained on a liquid diet. On day 1 of pregnancy the dams began the treatment protocol. On day 21 of pregnancy the rats were sacrificed and the fetuses removed. Gamma glutamyl transpeptidase (GGTP) activity was determined for liver and brain tissue from both the fetuses and the dams. GGTP activity in the EtOH/silymarin treatment groups did not differ significantly from that observed for the pair-fed control group. The observed GGTP activity levels for the EtOH-only group were significantly higher than those attained by the pair-fed control group. Although GGTP activity did not vary significantly with the quantity of PHYTO administered, as PHYTO dose was increased, GGTP activity decreased.

Alcohol consumption: biochemical and personality correlates in a college student population

The frequency of alcohol use among a subject population of 28 male and 60 female college students was assessed using the Student Alcohol and Drug Use Survey (STADUS). Data were also collected on personality traits as measured by the Sensation Seeking Scale V (SSSV) and the Eysenck Personality Questionnaire (EPQ). Finally, three biochemical variables were assessed: monoamine oxidase (MAO) activity, dopamine beta hydroxylase (DBH) activity, and testosterone levels. Among males, high SSSV scores, high testosterone levels, and low MAO activity contributed to the variance in alcohol use, whereas among females, a significant proportion of the variability in alcohol use was accounted for by high SSSV scores, high DBH activity, and younger age.

Prenatal exposure to ethanol retards the development of kindling in adult rats

The development of kindling was examined in adult rats exposed to ethanol prenatally. Pregnant Wistar rats were fed a liquid diet containing either 6.7% ethanol or pair fed an isocaloric equivalent. At birth, the litters were cross fostered to surrogate mothers. At 80 days of age, a bipolar electrode was placed either in the right basolateral amygdala or the right angular bundle of entorhinal cortex. Kindling stimulations were administered three times a day until each rat had exhibited three class 5 kindled motor seizures. The total number of kindling stimulations required to exhibit class 1 through class 5 motor seizures was significantly greater in the rats exposed to ethanol prenatally. Further, the retardation in kindling development was due to a slower progression from class 0 to class 1 kindled motor seizures. Progression between other stages was not different between the two groups. Similar results were obtained in both amygdala and angular bundle kindling experiments. Kindling is retarded in a similar fashion by partial destruction of the dentate granule cells of the hippocampal formation. Further, the pattern of dentate granule cell axonal projections to hippocampal CA3 pyramidal neurons is altered in rats exposed to ethanol prenatally. Taken together, these data suggest the possibility that a defect in the neuronal circuitry within the hippocampal formation of fetal alcohol rats may underlie a retardation in their kindling progression. This proposed defect may have functional implications related to learning deficiencies in rats and children exposed to ethanol prenatally.

Differential immune response in two handled inbred strains of mice

C57BL/10J and BALB/cJ mice, outfostered at birth to C3H/2Ibg dams were subjected to handling on days 1 through 20 of life. Their plaque forming cell (PFC) response to sheep red blood cells as adults on day 5 post-immunization was compared to the PFC response in non-handled control mice. The PFC response of handled C57BL/10J mice was significantly suppressed compared to the PFC response in non-handled mice while the response of the handled and non-handled BALB/cJ mice was not significantly different.

Fetoprotectivity of the flavanolignan compound siliphos against ethanol‐induced toxicity

Of the three flavanolignans that are found in silymarin (Silybum marianum [L.] Gaertn.), silybin is thought to be the primary therapeutic constituent. To test the capacity of silybin to protect the rat fetus from toxic effects of maternally ingested EtOH we did the following: Adult female rats were assigned to one of four groups; EtOH, EtOH/silybin, pair‐fed control, and chow fed control. Silybin was orally administered as Siliphos®, which is one part silybin to two parts phosphatidylcholine. All groups except the chow‐fed control were maintained on a liquid diet throughout pregnancy. On day 21 of pregnancy the rats were killed and the fetuses removed. Gamma glutamyl transpeptidase (GGTP) activity and glutathione (GSH) levels were determined for liver and brain tissue for both the fetuses and the dams. Maternal and fetal GGTP activity in the EtOH rats was significantly higher than that of pair‐fed controls, whereas the GGTP activity observed in the Siliphos®/EtOH rats was not elevated. Fetal mortality rates in the EtOH rats significantly exceeded those of all three other groups. Copyright

Effects of in utero administration of alcohol on alcohol sensitivity in adult rats.

In utero exposure to alcohol has been associated with many physical deficits and behavioral abnormalities. The purpose of these studies was to determine the effects of in utero administration of alcohol on behaviors related to tolerance and sensitivity to alcohol in adult rats. Pregnant rats were maintained on a liquid diet containing alcohol [35% ethanol-derived calories (EDC)] throughout pregnancy. Offspring manifested physical characteristics of Fetal Alcohol Syndrome. The 35% EDC group was able to stay on a wooden dowel longer and at higher blood alcohol concentrations than were pair-fed controls. Following a hypnotic dose of alcohol, rats in the 35% EDC group slept longer than pair-fed controls. A greater alcohol-induced hypothermic effect was seen in females in the 35% EDC group than in controls. Treatment did not affect rate of metabolism of alcohol. These studies suggest that in utero administration of alcohol may be a factor in determining an individuals sensitivity and tolerance to alcohol and possibly their preference for alcohol.

Subcellular and regional localization ofγ-glutamyl transpeptidase in sheep brain

Studies of the subcellular distribution ofγ-glutamyl transpeptidase from sheep brain by discontinuous sucrose density gradient centrifugation showed that 40% of the transpeptidase activity associated with the mitochondrial-synaptosomal fraction was localized with the synaptosomal-enriched fraction. The microsomal fraction was found to have the highest specific activity whenγ-glutamylp-nitroanalide was used as substrate. This activity, however, represented only 5% of the totalγ-glutamyl transpeptidase activity. Approximately 90% of the total enzyme activity was apparently associated with the fraction containing cell debris and membrane fragments.The 160,000g supernatant fluid (soluble supernatant fraction) represented the least total activity, with only 1.2% recovery; however, this fraction contained two apparent forms of the enzyme. One form had a highKmand the other a lowKm for the substrate,γ-glutamylp-nitroanilide.It was observed that the enzymeγ-glutamyl transpeptidase was not evenly distributed in all areas of brain when the homogenate was used as the enzyme source. The brain region with the highest enzyme activity was the thalamus, which was able to form 1.10 μmolp-nitroanaline/min/g wet brain tissue. The cortex was found to have the lowest activity. The 40,000g supernatant fluid from each region, however, exhibited only slight distribution differences.

Adjudicated adolescent males: measures of urinary 5-hydroxyindoleacetic acid and reactive hypoglycemia

Abstract A psychological model identified as the ‘low serotonin syndrome’ has been posited to explain the associated between certain biological characteristics such as low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and reactive hypoglycemia; and aggressive, violent, or impulsive behavior. Thirty-seven male adolescents adjudicated for violent offenses were compared with 37 middle school adolescents on the following measures: urinary 5-HIAA levels, response to the glucose tolerance test (GTT), and scores on the Impulsive Sensation Seeking (ImpSS) and Aggression-Hostility (AGG-Host) subscales of the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). The mean urinary 5-HIAA value in the adjudicated subjects was significantly lower than the 5-HIAA mean for the middle school controls. In response to the GTT, the mean blood glucose nadir recorded for the adjudicated group was also significantly lower than the glucose nadir mean obtained from the control subjects. Scores on the ImpSS subscale did not differ significantly whereas the adjudicated adolescents scored significantly higher on the Agg-Host subscale than did the control subjects.

Effects of tricyclic antidepressants on platelet monoamine oxidase activity

The eight subjects in this study were diagnosed as having primary or secondary depression and were treated with amitriptyline, 100 to 300 mg/day. Activity of platelet monoamine oxidase (MAO), an enzyme responsible for the degradation of biogenic amines, was determined before and after treatment with amitriptyline. Pretreatment values for MAO activity ranged from 17.94 to 44.89 U. After amitriptyline the values ranged from 0.66 to 41.94 U, a mean decrease of 50.2%. These results are consistent with the hypothesis that the tricyclic antidepressants act, at least in part, by inhibition of MAO.