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Biomedical subjects

B C Dudek

Publications and source records attributed to B C Dudek.

At least 37 records · Page 2Linked to original sources
PubMed1989

Ethanol teratogenesis in selectivity bred long-sleep and short-sleep mice: a comparison to inbred C57BL/6J mice.

Sensitivity to alcohol may influence the severity of ethanol teratogenesis. To examine this hypothesis, the teratogenic effects of ethanol were compared in Long-Sleep (LS) and Short-Sleep (SS) mice, selectively bred for differences in ethanol-induced narcosis. Inbred C57BL/6J (B6) mice were included to confirm previously reported teratogenic effects using our own treatment regimen and standard assessment technique. Intragastric administration of ethanol (5.8 g/kg) on Days 9 and 10 of pregnancy resulted in growth retardation and an increase in prenatal mortality in LS litters but not in SS litters. Therefore, alcohol sensitivity plays a role in the severity of prenatal alcohol effects. B6 mice showed more ethanol teratogenicity than either LS or SS mice, even though maternal blood ethanol levels were similar across genotypes. This result suggests genetic variations other than alcohol sensitivity also influence ethanol teratogenesis.

Animals↗
PubMed1986

Naturalistic behavioral assessment of anxiolytic properties of benzodiazepines and ethanol in mice.

Effects of chlordiazepoxide (CDZ), flurazepam (FLU) and diazepam (DZP) were assessed in mice by observation of digging behavior in an escape task. Reliable effects on escape latencies and number of exploratory head pokes were detected at 2 mg/kg for CDZ and FLU. DZP produced dose-dependent effects at 0.2, 0.4 and 0.6 mg/kg. Ro 15-1788 antagonized the effects of DZP (0.6 mg/kg). Ethanol (0.75 and 1.5 g/kg) produced effects similar to those of the benzodiazepines. The dynamics of this naturalistic behavior avoid the need for direct aversive stimulation or food/water deprivation to set up an approach-avoidance or conflict test. Combined with a multivariate (discriminant) analysis, the approach provides a sensitive assessment of anxiolytic drug activity.

Animals↗
PubMed1984

Stimulant and depressant properties of sedative-hypnotics in mice selectively bred for differential sensitivity to ethanol.

A genetic analysis of sedative-hypnotic response in selectively bred Long-Sleep (LS) and Short-Sleep (SS) mice showed LS mice to be more depressed by acetaldehyde, ethanol (ETOH), and t-butanol, but less sensitive to pentobarbital. Intermediate inheritance was shown by the two reciprocal F1 hybrids for the alcohols, but dominance to the LS genotype occurred for the aldehyde and the barbiturate. At several subhypnotic doses of ETOH in two experiments, LS mice showed less locomotor stimulation and greater disruption of coordination than the SS mice. The two reciprocal F1 hybrids did not differ from one another and had dose-response curves intermediate to the two parental lines. Study of the effects of t-butanol on locomotor activity revealed a pattern of line differences similar to that for ETOH. The genetic selection for LS and SS mice appears to have differentiated loci that pleiotropically influence a variety of behavioral responses to alcohols.

Analysis of Variance↗
PubMed1984

Apomorphine effects on behavioral response to ethanol in mice selectively bred for differential sensitivity to ethanol.

Two lines of mice selectively bred for differences in response to a hypnotic dose of ethanol were administered apomorphine alone or in combination with ethanol. When administered by itself, apomorphine produced similar dose-dependent depression of locomotor activity and increases in stereotypy in the two lines. Doses of apomorphine (0.5 microM/kg and 2 microM/kg) thought to bind only presynaptic dopamine receptors blocked the slight locomotor activation to 1.5 g/kg ethanol in the ethanol-sensitive Long-Sleep (LS) mice; in the ethanol-insensitive Short-Sleep (SS) mice which show marked activation to all subhypnotic doses of ethanol, these doses of apomorphine only attenuated the activation. A higher apomorphine dose (8 microM/kg) antagonized the locomotor depressant effects of 2.0 and 2.5 g/kg of ethanol in LS mice but did not alter the shape of the SS ethanol dose response curve for locomotor activity. Apomorphine (2 and 8 microM/kg) potentiated ethanol-induced loss of the righting reflex in LS mice in a dose dependent fashion, but did not alter this soporific effect of ethanol in SS mice. These findings extend the data base suggesting a role for dopamine both in the mechanism(s) differentiating the LS and SS mice and the stimulant and intoxicating properties of ethanol.

Animals↗
PubMed1983

The role of associative factors in tolerance to the hypothermic effects of morphine in mice.

Associative learning theories of drug tolerance emphasize the importance of stimuli which predict drug administration. One such model holds that drug tolerance is due to the development of a conditional response (CR) which is directionally opposed to the unconditional response (UCR) to the drug. By virtue of their opposing natures, the overlapping occurrence of CR and UCR is seen as a diminished response, i.e., tolerance. The present experiments tested the predictions of this model using two doses of morphine, and included truly random controls to examine the role of excitatory and inhibitory conditioning in tolerance. Tolerance was greatest in mice administered morphine in the context of stimuli previously paired with drug administration, intermediate in random controls, and least or absent in mice administered the drug in the presence of cues paired with vehicle injections. No direct evidence of a compensatory CR which could offset morphine's hypothermic effect was obtained in placebo test sessions, nor was evidence for such a response obtained in cross-drug tests with amphetamine and apomorphine.

Animals↗
PubMed1983

Genetic influences on digging behaviors in mice (Mus musculus) in laboratory and seminatural settings.

Digging behaviors of several inbred strains of laboratory mice and some of their crosses were examined in three contexts. In laboratory burrow boxes, C57BL/6Abg mice constructed more sophisticated burrow systems than did BALB/cAbg mice. Their F1 hybrids built burrow systems more complex than either parental strain. The same pattern of genetic influence was observed in an outdoor pen. In an escape task that required digging, BALB/c mice escaped more quickly than did C57BL/6 mice; their F1 hybrids showed dominance toward the BALB/c phenotype. These results indicate that behavioral polymorphisms in digging behavior, which may relate to habitat selection, have a genetic basis. The dominance and overdominance toward the better digging parental strain in each type of task suggest the possible evolutionary importance of these digging behaviors.

Animals↗
PubMed1983

Locomotor stimulant and intoxicant properties of methanol, ethanol, tertiary butanol and pentobarbital in Long-Sleep and Short-Sleep mice.

Methanol, ethanol, t-butanol and pentobarbital all produced marked dose dependent activation of locomotor activity in Short-Sleep mice which were selectively bred for relative insensitivity to the hypnotic properties of ethanol. The locomotor activity of alcohol sensitive Long-Sleep mice was depressed in a dose dependent fashion by all four drugs. Simultaneous assessment of intoxication in a grid test indicated that all four drugs disrupted coordination, in a dose dependent manner, to a greater degree in Long-Sleep mice than in Short-Sleep mice. The line differences in response to all alcohols was greater than for pentobarbital, indicating that the previous assumption of specificity of the selection for alcohols may be a question of degree rather than a qualitative effect.

Alcoholic Intoxication↗
PubMed1980

Effects of gamma-butyrolactone, amphetamine, and haloperidol in mice differing in sensitivity to alcohol.

Gamma-butyrolactone (GBL) induced longer loss of righting reflex in mice (LS-line) selectively bred for greater sensitivity to ethanol than in less sensitive SS-line mice. GBL also induced a three-fold greater increase of brain dopamine levels in LS than in SS mice. Among three inbred strains, GBL-induced loss of righting reflex was greater in BALB/c, and greater in DBA/2 than in C57BL/6 mice. A low dose of GBL produced biphasic effects on locomotor activity. Both an initial depressant action and a later increase in activity were greater in LS than in SS mice. These GBL effects on activity were modified in a genotype-dependent fashion by amphetamine. Results of these experiments as well as greater catalepsy-inducing properties of haloperidol in SS mice suggest that genotypic influences on motor reactivity to ethanol may be modeled by GBL effects on brain dopamine systems.

4-Butyrolactone↗
PubMed1978

Task-dependent genetic influences on behavioral response of mice (Mus musculus) to acetaldehyde.

Acetaldehyde was employed as a pharmacological agent in behavioral tests designed to assess genetic influences upon response to the drug. When used as a poison in a conditioned taste aversion study, acetaldehyde was more effective at inducing aversions in DBA/2J mice than in C57BL/6J mice. In another experiment, however, C57 mice were more affected than were DBA mice by acetaldehyde effects on loss of righting reflex. Implications for postulated genetic control of ethanol preference and neurosensitivity are discussed.

Acetaldehyde↗
PubMed1976

Salsolinol differentially affects mice selected for sensitivity to alcohol.

Salsolinol, a compound putatively formed following alcohol ingestion, differentially decreased the activity of lines of mice after 18 generations of genetic selection for alcohol sensitivity. Low doses of salsolinol produced significantly lower activity levels in the alcohol-sensitive long-sleep (LS) line than in the alcohol-insensitive short-sleep (SS) line. A hypnotic dose of salsolinol induced significantly longer sleeptimes in the LS line than in the SS line. Results are interpreted as supporting the hypothesis that salsolinol-like substances may mediate some of the effects of alcohol on the central nervous system.

Acetaldehyde↗
PubMedDate not supplied

Behavioral effects of salsolinol and ethanol on mice selected for sensitivity to alcohol-induced sleep time.

Two lines of mice, selected for differential sensitivity to alcohol, were tested following intracisternal administration of salsolinol, a compound putatively formed following ethanol ingestion. Both lines showed dose-dependent decreases in activity following salsolinol. When injected with ethanol, alcohol-insensitive short-sleep (SS) mice increased in activity while alcohol-sensitive long-sleep (LS) mice showed no change. Measures of coordination, taken following ethanol, demonstrated that LS mice were more incapacitated than SS mice. Salsolinol effects are discussed with reference to possible adrenergic blocking actions. Genetic differences in sensitivity to the incoordinating effects of alcohol were found.

Acetaldehyde↗
PubMedDate not supplied

An evaluation of the role of ethanol clearance rate in the differential response of long-sleep and short-sleep mice to ethanol.

Ethanol (ETOH) clearance rates were determined in Long-Sleep (LS) and Short-Sleep (SS) mice, which were selectively bred for differential soporific response to ETOH. Determination of blood ethanol levels at 45 min intervals following administration of 3.8 g/kg IP indicated that SS mice clear ETOH at a faster rate. Repeatedly sampled mice of each line cleared ETOH more slowly than those where samples were taken only once. A second experiment utilized pairs of LS and SS mice matched on body weight. These were treated with one of several doses of ETOH, and duration of loss of the righting reflex measured for one member of the pair. Blood ETOH levels were determined in samples taken from both members of the pair when the tested member regained the righting reflex. LS mice had small but consistently higher blood ETOH levels in these pairs. The magnitude of the differences between the LS and SS mice in these experiments indicate that clearance rate differences can account for only a small portion of the differences in behavioral responses of these mice to ETOH.

Animals↗
PubMedDate not supplied

A comparison of ethanol absorption and narcosis in long- and short-sleep mice following intraperitoneal or intragastric ethanol administration.

Blood ethanol concentrations (BEC) were determined in Long-Sleep (LS) and Short-Sleep (SS) mice during a 30 min period following ethanol (ETOH) administration. Absorption of ETOH was rapid and followed a similar time course in the two lines after intraperitoneal (IP) administration of 3.8 or 4.5 g/kg. Following intragastric (IG) administration, slower absorption and lower peak BECs were noted in both lines, but in LS mice this effect was more pronounced. The two routes of administration were not effective in altering duration of loss of the righting reflex (LRR), or waking BECs following 4.5 g/kg ETOH. LS mice had the expected longer LRR durations and lower BECs at waking than did SS mice. Differences in absorption rate and peak BEC are concluded to be unrelated to ETOH neurosensitivity in these mice.

Animals↗
PubMedDate not supplied

Ethanol teratogenesis in mice selected for differences in alcohol sensitivity.

Long-Sleep (LS) and Short-Sleep (SS) mice, selectively bred for differences in ethanol-induced narcosis, were administered ethanol (2.9, 4.0, 4.5, or 5.0 g/kg) twice per day during the period of organogenesis. On gestation day 18, the dams were sacrificed and the uterine horns were examined for live, dead, and resorbed fetuses. Live fetuses were weighed and assessed for either skeletal or soft tissue anomalies. The 5.8 g/kg/day dose had no effect on prenatal mortality, litter size, body weight, or number of physical anomalies in either line. However, the alcohol-sensitive LS mice exposed to ethanol doses of 8.0 g/kg/day or more evidenced decreased body weights while weights for the alcohol-insensitive SS mice differed from controls at only the highest dose tested. The incidence of skeletal variants was increased in the LS mice exposed to the 10 g/kg/day ethanol dose. These results indicate genetically-mediated alcohol sensitivity increases susceptibility to some of the fetotoxic effects of in utero alcohol exposure.

Animals↗
PubMedDate not supplied

Responses to ethanol challenge in long- and short-sleep mice prenatally exposed to alcohol.

Individual sensitivity to alcohol may influence the severity of functional deficits due to prenatal alcohol exposure. To examine this hypothesis, Long-Sleep (LS) and Short-Sleep (SS) mice, selectively bred for differences in ethanol-induced narcosis, were intubated with either 2.9 g/kg ethanol (E) or an isocaloric amount of sucrose (S) twice per day on days 7 through 15 of pregnancy. An untreated control group (C) was maintained for each line. Offspring were fostered to lactating Rockland-Swiss mice at birth. Males and females from each litter were challenged with an acute dose of ethanol (3.8 g/kg) at 30 days of age. Measures of sleep time duration, waking blood ethanol concentrations (BEC), rectal temperatures, heart rate, and ethanol clearance were obtained to examine whether the acute effects of ethanol are altered by prenatal alcohol exposure. Prenatal alcohol exposure did not differentially affect responses to ethanol challenge within either genotype. Ethanol-induced hypothermia, heart-rate depression, and sleep time did differ between genotypes, with LS more affected than SS mice. Ethanol clearance rates were faster for SS than LS mice. These results suggest postnatal pharmacological responses to acute ethanol challenge are not altered by prenatal alcohol exposure in LS and SS mice. Prenatal alcohol-exposed offspring of both mouse genotypes showed lower average heart rate responses than controls, suggesting this measure may be a sensitive indicator of prenatal alcohol effects in mice.

Animals↗