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Biomedical subjects

L W Means

Publications and source records attributed to L W Means.

53 records · Page 3Linked to original sources

Prenatal ethanol exposure fails to affect stimulus reactivity in the rat.

Three groups of male Long-Evans rats, that were the offspring of dams maintained throughout pregnancy on a liquid diet in which 35% of the calories were derived from ethanol, pair fed an isocaloric liquid diet that had maltose-dextrin substituted for the ethanol, or maintained on lab chow and water were used as subjects. All subjects were nursed by foster mothers maintained on lab chow and water throughout pregnancy and lactation. The groups were not found to differ on open field activity or number of approaches to four stimulus objects in an open field at 26-30 days of age, on spontaneous alternation at 50-55 days of age or on response to a novel alley at 55 days of age. It was concluded that in the rat, prenatal ethanol exposure does not result in demonstrable changes in responsivity to stimuli in rats tested after 26 days of age.

Aging↗

The effect of embryonic ethanol exposure on detour learning in the chick.

To examine the effects of embryonic ethanol exposure on survivability, posthatch growth and detour learning, 4 groups of 30 fertile black sex-linked eggs were given 200 microliter injections of a solution of water and 0.0, 12.5, 37.5 or 50.0% (groups IC, L, M and H, respectively) ethanol (v/v) immediately preceding incubation. A fifth group of 33 eggs served as noninjected controls (NC). The results demonstrated that compared to group NC, a smaller percentage of groups M and H hatched and survived for behavioral testing, and that group H required more trials to reach criterion on the detour learning problem than did group IC. It was concluded that the teratogenic effects of ethanol are robust with respect to species and that the chick is an excellent model for studying some developmental and behavioral effects resulting from embryonic ethanol exposure.

Animals↗

Embryonic ethanol exposure impairs detour learning in chicks.

Six groups of 30 fertile eggs each were injected with 200 microliters of either sterile water or a 37.5% (v/v) ethanol solution immediately before incubation or on days 7 or 14 of incubation. Regardless of day of injection, the ethanol groups had a lower proportion of chicks who completed pipping and hatching. Of the chicks surviving to pip and hatch, the group injected with ethanol immediately before incubation was delayed significantly in pipping compared to the other ethanol-injected groups and to the group injected with water immediately before incubation (p less than 0.05 in all cases). Also, compared to the chicks injected with water, the chicks in all ethanol groups required more trials to attain criterion on a detour learning task when tested 7-10 days after hatching (p less than 0.05).

Animals↗

Prenatal exposure to cocaine. I: Effects on gestation, development, and activity in Sprague-Dawley rats.

Sperm-positive Sprague-Dawley rats received one of four treatments for 20 days beginning within 24 hours of conception. One group received subcutaneous injections of 15 mg/kg cocaine twice daily (Cocaine-D); a second group received 15 mg/kg cocaine twice daily for two consecutive days at 5-day intervals (Cocaine-I); a third group received normal saline twice daily (Saline); and a fourth group received 1.5 mg/kg amfonelic acid (AFA), a dopamine reuptake inhibitor, once daily. Cocaine-D, Cocaine-I, and AFA dams were fed ad lib. An attempt was made to pair-feed the Saline dams with the Cocaine-D dams; however, the Saline dams did not eat as much as the Cocaine-D dams which resulted in dams in all groups essentially eating ad lib. The Cocaine-D pups showed a slightly delayed righting behavior and neophobia at 30 days of age, as evidenced by hypoactivity during the first 15 min of a 6-h activity test. The Cocaine-I pups were hypoactive during the 3-h dark phase of the 6-h activity test when tested at 30 days of age. These effects did not occur in the offspring exposed to AFA, a potent dopamine uptake inhibitor and CNS stimulant which indicate that one or more other sites for cocaine action may combine for its effects on the developing fetus.

Animals↗

Prenatal exposure to cocaine. II: Effects on open-field activity and cognitive behavior in Sprague-Dawley rats.

Pregnant rats received subcutaneous injections of 15 mg/kg of cocaine twice daily (Cocaine-D), twice daily for two consecutive days at 5-day intervals (Cocaine-I), 0.9% saline (Saline) twice daily, or 1.5 mg/kg amfonelic acid (AFA) daily from gestational days 1-20. Offspring were tested for: rates of spontaneous alteration at postnatal days (PND) 32, 35, 40, and 45; acquisition and retention performance on a water maze task beginning at PND 30 and 60; entrance into and activity in an open-field apparatus at PND 60 and 180. The Cocaine-D offspring were less likely than Control offspring to enter the open field when tested at PND 60. The Cocaine-I offspring were hyperactive in the open-field apparatus when tested at PND 60. The drug treated offspring did not differ from the Saline control animals on all other measures. The failure of the Cocaine-D animals to enter the open field is consistent with neophobic behavior that we have observed before in rats exposed in utero to cocaine.

Analysis of Variance↗

Place DMTS water-escape with direct placement or response information runs.

A two-choice, spatial delayed matching-to-sample (DMTS) water-escape task has proved to be a valuable of assay of trial-dependent memory. The task involves giving rats trials consisting of a forced-choice information run and a free-choice test run that are separated by a 5-m retention interval. Two experiments were conducted to determine the importance of making a complete response (R), partial response (P), or no response (NR; direct placement on escape platform) during the information "run" on acquisition and the subsequent performance of the task. Most of the naive, male, Sprague-Dawley rats were capable of attaining a 90% correct choice criterion when trained with P or NR information runs, but rats trained with R information runs required fewer trials to attain criterion and had shorter escape latencies during the criterion trials. Rats in all three groups showed significant retention at retention intervals as long as 1 h. Rats overtrained on the task with R information runs were subsequently able to perform the task at above chance level, regardless of the type information run given on the trial, but performed more accurately on trials where they made P or R information runs. Thus, rats use and perform better on place DMTS when allocentric environmental and egocentric response-associated cues are both available.

Animals↗

Effects of pregnancy and progesterone on the consumption of ethanol by the high ethanol preferring (HEP) rat.

A significant fraction of women continue to drink heavily during pregnancy, which is associated with the fetal alcohol syndrome, alcohol-related birth defects, alcohol-related neurodevelopmental disorder, and spontaneous abortion. The objective of this study was to determine whether the selectively bred genetic drinking Myers High Ethanol Preferring (HEP) rat would continue to drink through pregnancy. Rats from the F7 generation were screened by a 10-day 3-30% (v/v) ethanol concentration 'step up' procedure in order to determine the concentration which resulted in maximal drinking with an ethanol solution to total fluid ratio closest to 0.5. After baseline drinking of the preferred concentrations was established, female HEP rats were randomly selected for mating and their ethanol bottles were removed. Upon finding a 'sperm plug', male rats were removed and the ethanol was returned. A second group received injections of progesterone in sesame oil beginning with a 1.0 mg/kg/day dose which was increased to 3.0 mg/kg/day on gravid days (GD) 5-20. Vaginal smears confirmed that progesterone rendered the rats anoestrous. Neither pregnancy nor progesterone changed either the amount or proportion of ethanol consumed compared to the baseline period. The rats drank an average of 8.4 g/kg daily throughout pregnancy. A sharp drop in food intake was noted the day after mating. Beginning on GD 13, it was observed that pregnant rats showed a marked increase in the variance for proportion of ethanol consumed and body weight. Subsequently, only one of the eight impregnated rats successfully delivered a litter. The ethanol solution was removed and these rats mated again: seven of the eight rats delivered litters. These two findings suggest that the pregnant females must have begun to lose their litters on or after GD 13. Further, pregnancy does not affect the consumption of ethanol in the HEP rat. In addition, due to the fact that drinking by HEP rats during pregnancy leads to such a high rate of resorption of the fetus, this hybrid strain may also constitute a useful model for the study of alcohol-induced spontaneous abortion.

Alcohol Drinking↗

Prenatal ethanol exposure in rats does not alter maze exploration or impair visual discrimination with or without distracting stimuli.

The effects of in utero exposure to ethanol on maze exploration and visual discrimination and reversal with and without distracting tactile stimuli present were examined in rats. Three groups were compared on all measures. An ethanol treated group was the offspring of dams receiving a liquid diet throughout pregnancy with 35% of the calories supplied as ethanol. Subjects in a pair-fed group were the offspring of dams fed the same diet except that the caloric equivalent of maltose-dextrin was substituted for the ethanol. Subjects in a third group were the offspring of dams fed ad lib lab chow and water throughout pregnancy. All pups were nursed by foster mothers who received ad lib lab chow and water throughout pregnancy and nursing. Relative to the control groups, the ethanol treated group was not found to be significantly more active in the maze at 41-45 days of age or deficient in visual discrimination or reversal with or without the distracting stimuli present at 46-77 days of age. These results are consistent with many studies suggesting that behavioral deficits resulting from in utero ethanol exposure become less evident with age.

Animals↗

Hyperresponsiveness to methylphenidate in rats following prenatal ethanol exposure.

Rats exposed in utero to ethanol are hyperresponsive to methylphenidate when tested as neonates or adults. Long-Evans rats were maintained on liquid diets containing either ethanol or maltose-dextrin (35% of total calories) or on lab chow and water throughout pregnancy. Male offspring, who were raised by foster mothers maintained on lab chow and water throughout pregnancy and lactation, were used in two experiments to examine the effects of methylphenidate on activity. In Experiment 1, a time-sampling procedure revealed that methylphenidate (0, 1, 2 & 4 mg/kg) increases the frequency of ambulation in young (26-38 day old) ethanol-treated offspring more than in control offspring. In Experiment 2, an open-field procedure revealed that methylphenidate (0, 2, 4, 6 & 8 mg/kg) produces greater increases in number of squares covered and the total duration of ambulation during 5-min tests in adult (100-184 day old) offspring treated prenatally with ethanol than in control offspring. Both studies revealed that the hyperactivation effect increases with increased doses of methylphenidate.

Animals↗

Behavioral effects of prenatal exposure to nicotine in guinea pigs.

Nicotine (3 mg/kg SC) administered twice daily throughout pregnancy to guinea pigs resulted in offspring that were behaviorally deficient both as neonates and adults. The nicotine-treated offspring showed reduced spontaneous alternation both as neonates and adults. Also, the nicotine-treated offspring were less likely to enter a novel alley as neonates and were deficient on brightness discrimination and reversal as adults.

Animals↗