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H C Becker

Publications and source records attributed to H C Becker.

66 records · Page 4Linked to original sources
PubMedDate not supplied

Effects of Ro 15-4513 and ethanol on operant behavior of male and female C57BL/6 mice.

Although the partial benzodiazepine receptor inverse agonist, Ro 15-4513, counteracts many ethanol effects, its effect on operant behavior or on ethanol-induced changes in this behavior, remains controversial. In this study, we examined the effects of Ro 15-4513, ethanol, and their interaction on behavior maintained by an FR 20 schedule of food reinforcement. Ro 15-4513 (1.0-4.0 mg/kg) and ethanol (1.5-3.0 g/kg) reduced lever-responding of both male and female mice. The disruptive effect of Ro 15-4513 was of short duration (approximately 10 min), and was greater in male than in female mice. Under equivalent dose and time parameters, ethanol disrupted behavior of both sexes to the same extent. In spite of the disruptive effects of both drugs when given alone, when given after ethanol and prior to testing, Ro 15-4513 attenuated the disruptive effects of ethanol in male mice. The present study extends previous reports by documenting: (1) that the disruptive effect of Ro 15-4513 on mice is of very short duration and occurs at lower doses than previously reported; (2) that, in spite of being disruptive itself, Ro 15-4513 can attenuate the disruptive effects of ethanol on schedule controlled behavior; and (3) that gender is an important consideration in determining the effects of this compound.

Animals↗
PubMedDate not supplied

The effect of prenatal ethanol exposure on scentmarking in the C57BL/6J and C3H/He mouse strains.

In utero exposure to ethanol has been shown to alter sexually dimorphic behaviors in rats. However, it is not clear whether this phenomenon is robust in other species, such as the mouse, which is sensitive to ethanol-induced birth defects. Further, it is not known whether significant differences exist across murine strains. If similar to the classic teratogenic effects of ethanol, it would be expected that strain differences in sensitivity should be evident, with some strains demonstrating an alteration in sexually dimorphic behavior and other strains demonstrating little or no effect. As a first attempt to address these issues, we have examined two mouse strains widely used in prenatal alcohol research, the inbred C3H/He and C57BL/6J strains. Scentmarking was selected as the behavior of interest. It is robustly sexually dimorphic in the rat and mouse, with males marking more than females and preliminary reports have demonstrated that in utero ethanol exposure reduces this behavior in the male rat. In the mouse strains selected for study, pregnant females were provided with either a liquid diet consisting of 25% ethanol-derived calories or pair-fed an isocaloric liquid diet from gestation days 6-18. An additional control group was included which was fed laboratory chow ad lib throughout gestation. Male and female offspring of each strain were tested for scentmarking at 65-75 days of age. As expected, results showed that the effect of prenatal ethanol exposure on scentmarking varied with both strain and sex. In the C3H/He strain, scentmarking was reduced significantly in male ethanol-exposed offspring (i.e., the males were feminized).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Reduced sensitivity to the effects of clonidine on ethanol-stimulated locomotor activity in adult mouse offspring prenatally exposed to ethanol.

Prenatal exposure to ethanol (EtOH) alters developing catecholamine (CA) systems and acute sensitivity to the locomotor stimulant effects of EtOH. As an extension of previous work involving CA agents, this study addressed whether prenatal EtOH exposure influences central norepinephrine (NE) systems by examining the motoric effects of the direct alpha 2 adrenoreceptor agonist clonidine given alone and in combination with a low-dose stimulant challenge of EtOH. Standard lab chow or liquid diets containing either 25% EtOH-derived calories (EDC), or 0% EDC (pair-fed group) were given to pregnant C3H/He mice on gestation days 6-18. At 90 days of age, male offspring from each prenatal treatment group were monitored for 10 minutes in an open field following IP injections of clonidine (0, 0.0125, 0.025, or 0.05 mg/kg) and either EtOH (1.5 g/kg) or saline. In control offspring, clonidine suppressed locomotor activity and attenuated the stimulant response to EtOH in a dose-dependent fashion. In contrast, clonidine given alone did not suppress, but appeared to stimulate, activity in prenatal EtOH-exposed offspring. Furthermore, the ability of clonidine to attenuate the locomotor stimulant properties of EtOH was greatly reduced in prenatal EtOH-exposed animals. Taken together, these results indicate a shift to the right in the dose-response function for clonidine in prenatal EtOH-exposed offspring relative to control mice. Further, the results suggest that prenatal exposure to EtOH may result in long-lasting alterations in developing central NE systems, particularly presynaptic alpha 2 adrenoreceptor sensitivity.

Animals↗
PubMedDate not supplied

Effect of acute ethanol and cocaine administration on gestation days 14-17 in mice.

The teratogenic effects of the coadministration of alcohol and cocaine on gestation days 14-17 were investigated using an acute exposure model. Pregnant C57BL/6J mice were assigned randomly to treatment groups generated from a 2 (0 or 6 g/kg alcohol) x 2 (0 or 60 mg/kg cocaine) x 4 (day of treatment) factorial design. An untreated control group was also employed. On GD14, 15, 16, or 17, females were intubated with alcohol or an isocaloric solution and injected (SC) 10 min later with cocaine or saline. Litters were evaluated on GD19 following cesarean delivery. A significant number of females in the alcohol-only group treated on GD16 or GD17 delivered litters prior to GD19. The results indicated that, in general, prenatal alcohol exposure was associated with decreased fetal body weight and suggested a possible increase in malformations of vascular origin. Cocaine and the alcohol/cocaine interaction did not affect the outcome variables in any reliable manner. Thus, with the animal model employed, cocaine did not exert teratogenic effects on its own nor did it influence alcohol-induced teratogenesis.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Cocaine does not influence the teratogenic effects of acute ethanol in mice.

The teratogenic effects of the coadministration of alcohol (ethanol) and cocaine to pregnant C57BL/6J mice were investigated using an acute treatment model on gestation day 10 (GD10). The day of mating was designated as GD1. Pregnant mice were assigned to treatment groups generated from a 3(0, 4, 6 g/kg alcohol) x 3 (0, 40, 60 mg/kg cocaine) factorial design to explore possible interactive effects of these commonly abused drugs. Females were treated on GD10 (alcohol gavage followed by SC cocaine injection) and their litters were evaluated on GD19 by cesarean delivery. Two additional free-fed groups, as well as a pair-fed group, were employed. Food and water intake was recorded in treated groups. Results indicated that only the high dose alcohol produced a significant decrease in fetal body weight and a significant elevation of the incidence of kidney and limb malformations. These effects could not be attributed to restricted food intake. Cocaine was not found to produce any significant perturbations of development, either alone or in combination with alcohol. These results suggest that acute prenatal cocaine exposure on GD10 does not produce teratogenic effects when administered alone or in combination with acute alcohol in C57BL/6J mice, at least under the present experimental conditions.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Effect of prenatal ethanol exposure on response to abrupt reward reduction.

The purpose of this study was to examine the effects of prenatal ethanol exposure on an appetitively-motivated behavioral task (consummatory negative contrast) that involves quantification of an animal's response to an abrupt, unexpected reduction in reward (sucrose solutions). Pregnant Long-Evans rats received isocaloric liquid diets containing either 35% or 0% ethanol-derived calories on days 6-20 of gestation. A pair-feeding procedure was employed, and a lab chow control group also was included. Adult male offspring from these three prenatal treatment groups were used for behavioral testing. Results indicated all groups exhibited suppressed responding subsequent to reward reduction. This effect gradually diminished in all prenatal treatment groups over several test sessions. While there was a numerical tendency for ethanol-exposed offspring to exhibit a smaller initial contrast effect (less response inhibition) and recover to control levels at a faster rate than the sucrose and lab chow control groups, this effect was not statistically significant. Thus, prenatal ethanol exposure does not appear to greatly influence the response to abrupt, partial reward reduction in adult rat offspring.

Animals↗
PubMedDate not supplied

Prenatal ethanol exposure alters sensitivity to the effects of apomorphine given alone and in combination with ethanol on locomotor activity in adult male mouse offspring.

Previous studies have indicated that prenatal ethanol (EtOH) exposure alters developing catecholamine (CA) systems and acute sensitivity to the locomotor stimulant effects of EtOH. The purpose of this study was to examine whether prenatal EtOH exposure influences the effects of the direct dopamine (DA) agonist apomorphine given alone as well as in combination with a low-dose stimulant challenge of EtOH. Standard lab chow or liquid diets containing either 25% EtOH-derived calories (EDC), or 0% EDC were given to pregnant C3H/He mice on gestation days 6-18. At 90 days of age, male offspring from each prenatal treatment group were monitored for 10 min in an open field following IP injections of apomorphine (0, 0.15, 0.3, 0.6, or 1.2 mg/kg) and either EtOH (1.5 g/kg) or saline. EtOH alone increased activity by 120-143% in all three groups of offspring. In control offspring, apomorphine dose-dependently decreased activity up to 74%-78% and blocked the stimulant effect of EtOH at all doses tested. However, in prenatal EtOH-exposed offspring, higher doses of apomorphine were significantly less effective in reducing both baseline and EtOH-stimulated activity compared to control mice. This effect is most likely not due to differences in pharmacokinetics, because blood EtOH concentrations were similar across apomorphine doses and prenatal treatment conditions. As such, these results support the hypothesis that prenatal exposure to EtOH alters acute sensitivity to the locomotor stimulant effects of EtOH, particularly under conditions in which CA systems mediating those effects are additionally challenged. In addition, the results suggest that prenatal EtOH exposure results in a long-lasting perturbation of central DA receptor sensitivity.

Animals↗
PubMedDate not supplied

Acute gestational cocaine exposure alone or in combination with low-dose ethanol does not influence prenatal mortality or fetal weight in mice.

The teratogenic effects of cocaine and ethanol were investigated using an acute treatment model of C57BL/6J mice treated on gestation day 15 (GD15) with evaluation on GD17. Females were intubated once with a subteratogenic dose of ethanol (0 or 4 g/kg) and injected subcutaneously twice, 1 h apart, with equal doses of cocaine HCl (0 or 60 mg/kg), for a final daily dose of 120 mg/kg. The first cocaine injection followed ethanol by 10 min. Blood ethanol levels (BEL) and plasma cocaine levels were determined, and pair-feeding was employed. The results revealed no group differences on pregnancy outcome. That is, maternal weight gain, total number of implants, prenatal mortality, and fetal body weight were not statistically different. No significant differences in BEL or plasma cocaine levels were found among the various treatment groups. These results suggest that, under these conditions, relatively high levels of cocaine (120 mg/kg, SC), given alone or in combination with subteratogenic doses of ethanol late in pregnancy, are not teratogenic in mice.

Animals↗
PubMedDate not supplied

Exacerbation of ethanol withdrawal seizures in mice with a history of multiple withdrawal experience.

Repeated ethanol withdrawal experience has been shown to result in an exacerbation of future withdrawal episodes. This sensitization of the withdrawal response has been hypothesized to represent a "kindling" phenomenon. We previously demonstrated that mice exposed to ethanol vapor for a total of 48 h exhibited more severe withdrawal seizures if the exposure was divided into three 16 h intoxication/8 h abstinence cycles than if the 48 h of exposure occurred in a single bout. The present study was designed to further characterize this model of ethanol withdrawal "kindling" and determine whether such a "kindled" response may be evident when withdrawal testing is conducted after an additional bout of intoxication that is the same for all groups. Adult C3H mice were chronically exposed to ethanol vapor in inhalation chambers for 40 h prior to withdrawal testing. Prior to this 40 h intoxication period, one group (Multiple Withdrawal; MW) received three cycles of 16 h ethanol vapor separated by 8 h abstinence; a second group (Single Withdrawal; SW) did not receive any ethanol exposure prior to the 40 h test cycle; a third group (Continuous Exposure; CE) received the same total ethanol exposure as the MW group (48 hr), but without interruption: and a control group (C) did not receive any ethanol treatment throughout the experiment. Blood ethanol levels following the 40 h bout of ethanol intoxication were 100-140 mg/dl for all ethanol-exposed groups. The severity of handling-induced convulsions during withdrawal was significantly greater in the MW group compared to CE and SW groups. These results suggest that differences in the severity of ethanol withdrawal seizures due to differences in prior withdrawal experience can be demonstrated even when later ethanol exposure patterns are equated. As such, the results provide further support for the "kindling" hypothesis of ethanol withdrawal.

Alcoholic Intoxication↗
PubMedDate not supplied

Repeated ethanol withdrawal experience increases the severity and duration of subsequent withdrawal seizures in mice.

Repeated ethanol withdrawal experience has been shown to result in an exacerbation of future withdrawal episodes. This sensitization of the withdrawal response has been hypothesized to represent a "kindling" phenomenon. The present study was designed to examine whether a systematic increase in the number of previous ethanol withdrawal experiences increases both the severity and duration of a subsequent withdrawal response. An established model of repeated ethanol intoxication/withdrawal was employed in which adult C3H mice were chronically exposed to ethanol vapor in inhalation chambers. In the first experiment, multiple withdrawal (MW) groups of mice received nine (MW x 9), six (MW x 6), or three (MW x 3) cycles of 16-h ethanol vapor separated by 8-h periods of abstinence prior to testing: a single withdrawal (SW) group was tested following a single bout of 16-h ethanol exposure; and a control (C) group did not receive any ethanol treatment throughout the experiment. In a second experiment, a group of mice (MW1-9) were repeatedly tested over nine cycles of withdrawal. A third experiment was designed to assess the effects of repeated pyrazole administration on the potentiated withdrawal seizure response. Results indicated a positive relationship between the number of previously experienced ethanol withdrawals and the severity and duration of a subsequent withdrawal episode. Blood ethanol levels were similar for all ethanol-exposed groups prior to withdrawal assessment. Further, the intensity of withdrawal seizures (handling-induced convulsions) progressively increased over nine cycles of intoxication/withdrawal and repeated testing did not significantly influence the development of this potentiated response. In addition, repeated administration of pyrazole did not appear to influence this withdrawal sensitization phenomenon. Collectively, these results provide further support for the "kindling" hypothesis of ethanol withdrawal.

Administration, Inhalation↗
PubMedDate not supplied

Effect of prenatal ethanol exposure on activity and shuttle avoidance behavior in adult C57 mice.

Although the morphological teratogenic actions of ethanol have been well established in mice, studies on the behavioral teratogenic effects of alcohol have been primarily conducted with rats. The purpose of this study was to examine the behavioral effects of prenatal alcohol exposure in C57 mice, a strain known to be highly sensitive to the teratogenic actions of ethanol. Pregnant mice were administered a liquid diet containing 25% ethanol-derived calories (EDC) from day 5 through day 18 of gestation. Control animals were pair-fed an isocaloric 0% EDC diet during the same period of time, with sucrose substituted for ethanol. At 23 days of age, offspring were tested for spontaneous locomotor activity in an open field. At 70 days of age, different offspring were tested in a shuttle-avoidance task. The results demonstrated that the 25% EDC progeny were more active than controls. In addition, prenatal alcohol exposure produced a deficit in acquisition and performance of a shuttle-avoidance task. Alcohol-treated offspring made fewer avoidance responses and required more trials to reach a criterion performance of 10/10 avoidances consecutively followed by at least 9/10 avoidances. These results importantly contribute to the development of an animal model of Fetal Alcohol Syndrome in which both the behavioral and morphological consequences of prenatal alcohol exposure may be assessed in the same species.

Animals↗