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Biomedical subjects

H C Becker

Publications and source records attributed to H C Becker.

At least 19 recordsLinked to original sources
PubMed1992

Effect of chlorpromazine and haloperidol on negative contrast.

Rats shifted from 32 to 4% sucrose consume substantially less of the 4% solution than animals that have not had prior experience with the 32% sucrose. This negative contrast effect was not substantially influenced by chlorpromazine (1, 3, and 5 mg/kg) or haloperidol (0.1, 0.5, and 1.0 mg/kg). Haloperidol decreased overall lick frequency, but this decrease occurred proportionately in shifted and unshifted rats, leaving contrast intact. The benzodiazepine flurazepam (5, 10, and 20 mg/kg), included as a positive control, reduced contrast at the two highest doses. The results suggest that neuroleptics do not disrupt consummatory contrast and that dopaminergic antagonists may not influence reward relativity.

Animals↗
PubMed1992

Aspirin pretreatment reduces ethanol withdrawal severity in a mouse model of binge drinking.

Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin, which inhibit prostaglandin (PG) synthesis, have a pronounced effect on a broad range of ethanol (EtOH) actions. Given this, it is somewhat surprising that NSAID treatment has not been found to alter major signs of ethanol withdrawal. To date, the only effect found has been indirect, that is, NSAID treatment reduces the efficacy of PG precursor administration in the treatment of ethanol withdrawal via the inhibition of PG formation. However, in those studies reporting negative results NSAID administration was delayed until EtOH withdrawal. Studies demonstrating NSAID-related attenuation of other actions of EtOH have typically employed a pretreatment paradigm in which NSAIDs are administered prior to, not after, ethanol exposure. Thus, it may be that the point in the ethanol exposure/withdrawal episode at which NSAIDs are administered could be crucial in determining their effects of the ethanol withdrawal syndrome. To address this issue, we employed a multiple-exposure "binge drinking" model. On each of 6 treatment days, male BALB/c mice were injected subcutaneously with either acetylsalicylic acid (ASA, 150 mg/kg) or the buffer vehicle, followed 1 h later by either ethanol (4.0 g/kg) or saline (0.9%) by gavage. Ethanol withdrawal severity, as measured by handling-induced convulsions, was determined 2, 4, 6, 8, 10, 12, and 24 h after EtOH gavage. ASA pretreatment was found to significantly reduce handling-induced convulsions in ethanol-intubated animals. In fact, the attenuation was of such a magnitude that the ASA-pretreated ethanol group did not significantly differ in withdrawal severity from non-ethanol-exposed controls. This effect was not likely due to ASA-related alterations in ethanol pharmacokinetics. These findings have relevance for the understanding of the basic mechanisms underlying ethanol dependence, as well as the potential role of PGs in this phenomenon.

Alcoholism↗
PubMed1992

Present state of diagnostic management in veno-occlusive dysfunction.

Pharmacocavernosometry and pharmacocavernosography are essential for the diagnosis of veno-occlusive dysfunction. Pressure fading obtained by cavernosometry correlates excellently with results of intracavernosal pharmacon testing. Venous drainage as visualized by pharmacocavernosography is essential for localization of the venous channels especially if venocorrective surgery is planned.

Erectile Dysfunction↗
PubMed1992

Venous surgery in veno-occlusive dysfunction: long-time results after deep dorsal vein resection.

Follow-up of patients 1 year after deep dorsal vein resection gives evidence of an approximate 50-60% success rate. A careful selection of only this small percentage of patients, in whom abnormal drainage through the penile dorsum is obvious, is mandatory. Men with an arterial cofactor have to be excluded or to be subsequently treated by intracavernosal autoinjection of vasoactive substances. Late results from our study demonstrate a further loss of sufficient erection, also in men considered as persistent success by us, in the subjective view of the patient and/or his sexual partner.

Adult↗
PubMed1991

Aspirin dose-dependently reduces alcohol-induced birth defects and prostaglandin E levels in mice.

The purpose of the present study was threefold. The first purpose was to determine if aspirin (ASA) decreases alcohol-induced birth defects in mice in a dose-dependent fashion. The second purpose was to see if the antagonism of alcohol-induced birth defects afforded by ASA pretreatment was related to dose-dependent decreases in prostaglandin E (PGE) levels in uterine/embryo tissue. The third purpose was to determine if ASA pretreatment altered maternal blood alcohol level. In experiments 1 and 2, pregnant C57BL/6J mice were administered ASA (0, 18.75, 37.5, 75, 150, or 300 mg/kg) on gestation day 10. One hour following the subcutaneous injection of ASA, mice received alcohol (5.8 g/kg) or an isocaloric sucrose solution intragastrically. In experiment 1 the incidence of birth defects was assessed in fetuses delivered by caesarean section on gestation day 19. In experiment 2 uterine/embryo tissue samples were collected on gestation day 10 1 hr following alcohol intubation for subsequent PGE analysis. In experiment 3 blood samples were taken at five time points following alcohol intubation from separate groups of alcohol-treated pregnant mice pretreated with 150 mg/kg ASA or vehicle. The results from the three experiments indicated that 1) ASA dose-dependently reduced the frequency of alcohol-induced birth defects in fetuses examined at gestation day 19, (2) ASA decreased the levels of PGE in gestation day 10 uterine/embryo tissue in a similar dose-dependent fashion, and 3) ASA pretreatment did not significantly influence maternal blood alcohol levels. These results provide additional support for the hypothesis that PGs may play an important role in mediating the teratogenic actions of alcohol.

Abnormalities, Drug-Induced↗
PubMed1991

RO15-4513 antagonizes the anxiolytic effects of ethanol in a nonshock conflict task at doses devoid of anxiogenic activity.

RO15-4513 is a partial benzodiazepine inverse agonist that has been reported to antagonize some of the biochemical and neurobehavioral actions of ethanol. However, whether this antagonistic action of RO15-4513 is dependent on the drug exerting its intrinsic (inverse agonist) properties is unclear at present. The purpose of the present study was to examine whether RO15-4513 was capable of antagonizing the anxiolytic effects of ethanol in a nonshock conflict task at doses that, by themselves, do not reveal the compound's intrinsic anxiogenic properties. The consummatory conflict task employed (negative contrast) involves quantifying how animals respond to an abrupt, unexpected reduction in reward (sucrose solution), and is particularly sensitive to the effects of anxiolytic agents, including ethanol. As previously demonstrated, depressed consummatory behavior engendered by reward reduction was significantly alleviated by ethanol (0.75 g/kg). This anxiolytic effect of ethanol, however, was antagonized dose dependently by RO15-4513 (0.1875-3.0 mg/kg). Only the highest dose of RO15-4513 (3.0 mg/kg) showed evidence of further response suppression. Lower doses of RO15-4513 tested did not exert an anxiogenic effect when given alone. Thus the antagonism of EtOH's anxiolytic (contrast-reducing) effects occurred at doses of RO15-4513 (0.375-1.5 mg/kg) that did not exhibit any intrinsic anxiogenic activity. As such, these results suggest that RO15-4513 interacts with the anxiolytic effects of ethanol in a nonadditive fashion in this test situation.

Animals↗
PubMed1991

Effects of Ro 15-4513 on ethanol discrimination in C57BL/6 mice.

Ro 15-4513, a partial benzodiazepine receptor inverse agonist, counteracts many of the effects of ethanol, however, its effects on ethanol discrimination in operant paradigms remains unclear. The present study examined the effects of Ro 15-4513 on ethanol discrimination by female C57BL/6 mice in a food-reinforced behavior-operant paradigm. Under the time and dosing conditions used in previous reports, Ro 15-4513 did not alter ethanol discrimination whether given prior to or after ethanol exposure. The drug did, however, attenuate ethanol discrimination for brief periods (less than 8 min) when injected after ethanol and at doses and postinjection times which also disrupted responding. The present study confirmed that Ro 15-4513 attenuated ethanol discrimination, but not to the extent as previously reported. The results indicate that postinjection time is a very critical factor in whether Ro 15-4513 attenuates ethanol discrimination.

Animals↗
PubMed1991

Effect of ibuprofen on alcohol-induced teratogenesis in mice.

The purpose of the present study was to examine the effect of the prostaglandin synthetase inhibitor ibuprofen (IBU) on the teratogenic actions of alcohol. On day 10 of pregnancy, C57BL/6J mice were injected subcutaneously with 25 mg/kg IBU or vehicle control. One hour later, the mice were intubated with 5.8 g/kg alcohol or an isocaloric control solution. A group injected subcutaneously with 150 mg/kg aspirin, followed by 5.8 g/kg alcohol 1 hr later, served as a positive control. The results showed that maternal alcohol treatment resulted in significantly decreased fetal weight and an increased number of fetuses with limb and kidney defects. Implantation sites and prenatal mortality were not affected. IBU did not have any effect on these dependent variables. IBU statistically antagonized the teratogenic effects of alcohol on fetal weight and dysmorphology. These effects, however, were not as marked as in the Aspirin-Alcohol positive control group. These results are discussed in the context of clarifying the role of prostaglandins in the etiology of alcohol-induced birth defects.

Abnormalities, Drug-Induced↗
PubMed1990

Indomethacin does not antagonize the anxiolytic action of ethanol in the elevated plus-maze.

The present study was designed to examine whether the prostaglandin (PG) synthesis inhibitor indomethacin (INDO) could antagonize the anxiolytic effects of ethanol (EtOH) in the elevated plus-maze test of anxiety. EtOH (1.6 g/kg) significantly increased the percentage of open arm entries and time spent on the open arms in both inbred C57BL/6J and outbred CD-1 mouse strains. However, this anxiolytic effect of EtOH was not significantly antagonized by pretreatment with INDO (5 and 10 mg/kg) in either strain. EtOH also significantly increased total arm entries in CD-1 mice, but not in the C57BL/6J strain. These data from C57BL/6J mice indicate that the low-dose stimulant properties of EtOH can be dissociated from the anxiolytic action of the drug in the plus-maze task. Finally, although INDO did not antagonize the stimulant effect of EtOH in the plus-maze task (in CD-1 mice), it did attenuate EtOH-induced stimulation of locomotor activity in an open-field arena. Taken together, these results suggest some specificity with regard to the role of PGs in mediating (or modulating) the neurobehavioral actions of EtOH, and further support the notion that the anxiolytic and stimulant effects of EtOH may be mediated by different mechanisms.

Animals↗
PubMed1990

Ethanol increases PGE and thromboxane production in mouse pregnant uterine tissue.

The teratogenic effect of ethanol in the C57BL/6J mouse can be attenuated by pretreatment with aspirin (ASA). One prominent effect of ASA is to inhibit prostaglandin (PGE) and thromboxane (TXB2) production. We examined the effect of in vivo ethanol exposure on PGE and TXB2 production in a uterine-embryo tissue sample of C57BL/6J mice either before or after in vivo ASA pretreatment on day 10 of gestation. Ethanol increased both PGE and TXB2 production by approximately 20%. ASA caused a marked reduction of PGE and TXB2 in both control and ethanol groups by approximately 80-90%. The mouse strain, gestation time, and study parameters used in this study were the same as in the previously reported ASA attenuation of the teratogenic effect of ethanol. Therefore, the present data add additional support to the hypothesis that prostaglandin and/or thromboxane production may be involved in at least some aspects of fetal alcohol syndrome.

Analysis of Variance↗
PubMed1990

Valproate potentiates and picrotoxin antagonizes the anxiolytic action of ethanol in a nonshock conflict task.

The purpose of this study was to examine the effects of the indirect GABA agonist valproate and the indirect GABA antagonist picrotoxin on the anxiolytic (anti-conflict) activity of ethanol in a behavioral conflict task that does not employ electroshock. This task (negative contrast) quantifies how animals respond to an abrupt, unexpected reduction in reward. Treatment with valproate alone did not elevated depressed behavior engendered by abrupt reduction in reward. However, when administered together with a sub-effective dose of ethanol (0.5 g/kg), valproate (50-200 mg/kg) dose-dependently potentiated the anxiolytic action of ethanol. Picrotoxin (2 mg/kg) antagonized the anxiolytic effects of a larger dose of ethanol (1.0 g/kg) given alone, as well as the ability of valproate to enhance the anxiolytic effects of smaller dose of ethanol (0.5 g/kg). As such, these data support a role for GABA in mediating the anxiolytic activity of ethanol.

Animals↗
PubMed1989

Effects of prenatal ethanol exposure in C57BL mice on locomotor activity and passive avoidance behavior.

The purpose of this study was to examine the long-term behavioral effects of prenatal ethanol exposure in C57BL mice. Pregnant mice received free access to a liquid diet containing 25% ethanol-derived calories (EDC) from gestation days 6 to 18. Control animals were pair-fed an isocaloric 0% EDC diet during the same period of time. An additional control group was included that was maintained on standard lab chow and water throughout pregnancy. At 30 days of age, female offspring were tested for spontaneous locomotor activity in an open field under two lighting conditions (dim or bright illumination). Male offspring were tested in a passive avoidance task at 25 days of age. The activity results demonstrated that the 25% EDC female progeny were more active than controls. This hyperactivity was observed under both lighting conditions, despite the fact that all groups evidenced suppressed activity when tested under bright lights. With regard to passive avoidance behavior, male EtOH-exposed offspring required a greater number of trials to reach criterion than controls. Additionally, they exhibited shorter latencies to enter the shock-associated chamber after receiving a single shock. Taken together, these results confirm our previous findings and demonstrate that C57BL mice are sensitive to both the deleterious behavioral and morphological consequences of prenatal ethanol exposure.

Animals↗
PubMed1989

Ethanol-induced locomotor stimulation in C57BL/6 mice following RO15-4513 administration.

The purpose of this study was to examine the effects of two partial benzodiazepine inverse agonists, RO15-4513 and FG-7142, alone and in combination with ethanol on locomotor activity in C57BL/6 mice. When administered alone, 1.5 g/kg ethanol did not significantly influence activity, confirming previous reports indicating this mouse strain is relatively insensitive to the excitatory properties of ethanol. RO15-4513 treatment also did not significantly influence locomotor activity when administered alone. However, coadministration of RO15-4513 (1.5-6 mg/kg) and ethanol markedly increased locomotor activity. Moreover, the unmasking of ethanol's stimulant action by RO15-4513 (6 mg/kg) was completely reversed by pretreatment with the benzodiazepine receptor antagonist RO15-1788. In contrast, FG-7142 (10-20 mg/kg) increased activity to the same extent in both saline and ethanol-injected mice. This effect was blocked by RO15-1788 pretreatment as well. Neither RO15-4513, FG-7142, nor RO15-1788 significantly influenced blood ethanol concentrations. It is suggested that RO15-4513 unmasked the stimulant effects of ethanol by virtue of its ability to antagonize the depressant properties of ethanol in C57BL/6 mice.

Animals↗
PubMed1989

The benzodiazepine receptor inverse agonist RO15-4513 exacerbates, but does not precipitate, ethanol withdrawal in mice.

RO15-4513, an imidazobenzodiazepine that has been reported to antagonize several behavioral and biochemical actions of ethanol, was given to C3H mice at various times during withdrawal from chronic (72 hours) continuous exposure to ethanol vapor. When administered immediately following chronic ethanol exposure, RO15-4513 (6 or 12 mg/kg) did not influence the withdrawal response. However, when given at subsequent times (3, 5, and 8 hours postethanol withdrawal), RO15-4513 significantly increased the severity of the withdrawal response in ethanol-exposed mice. Moreover, this exacerbation was completely reversed by pretreatment with the benzodiazepine receptor antagonist RO15-1788. Thus, these data indicate that the benzodiazepine inverse agonist, RO15-4513, is capable of exacerbating, but not precipitating, ethanol withdrawal.

Acoustic Stimulation↗
PubMed1988

Effects of the imidazobenzodiazepine RO15-4513 on the stimulant and depressant actions of ethanol on spontaneous locomotor activity.

The purpose of this study was to investigate the effects of the imidazobenzodiazepine RO15-4513, a partial inverse agonist at benzodiazepine (BDZ) receptors, on the stimulant and depressant actions of ethanol in mice. For comparative purposes, another BDZ inverse agonist, FG-7142, was examined as well. Neither RO15-4513 nor FG-7142 influenced the low-dose excitatory effects of ethanol on spontaneous locomotor activity. However, both RO15-4513 and FG-7142 significantly antagonized the depressant effects of ethanol, and this antagonism was completely reversed by pretreatment with the BDZ receptor antagonist, RO15-1788. These data suggest that RO15-4513 is capable of antagonizing only some of the behavioral effects of ethanol, and in particular, those responses to ethanol that are mediated by modulation of the GABA/BDZ-chloride channel receptor complex.

Animals↗
PubMed1988

PGE measurement in mouse embryos and uterine/embryo tissue.

Embryonic tissue of rodents and other species has been reported to produce prostaglandins (PG) of the E series during gestation. We attempted to establish the presence of PGE in C57BL/6J mouse embryos and peri-embryonic tissue as an initial step in examining the role of maternal ethanol treatment on PG production. Gestation day 10 embryos were found not to produce or degrade PGE. However, a tissue complex which included embryonic tissue, peri-embryonic membranes, placenta and uterus was capable of producing PGE from both endogenous and exogenous arachidonic acid. Furthermore, in vivo and in vitro aspirin was able to suppress PGE production from this tissue. It is concluded that gestation day 10 C57BL/6J mouse embryonic tissue, unlike that of rat, is not capable of measurable PGE production. However, uterine and peri-embryonic tissues, needed to support pregnancy, are capable of significant PGE production.

Analysis of Variance↗