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Biomedical subjects

M W Church

Publications and source records attributed to M W Church.

49 records · Page 3Linked to original sources
PubMedDate not supplied

Prenatal alcohol exposure attenuates pentylenetetrazol-induced convulsions in rats.

Female rats prenatally exposed to alcohol were tested at 35 days of age for susceptibility to pentylenetetrazol (PTZ)-induced convulsions. There was a significant dose-response effect of PTZ. Contrary to expectations, alcohol-exposed females were slightly but still significantly less convulsion-prone than pair-fed controls. These results suggest prenatal alcohol exposure reduces the susceptibility to convulsions in rats.

Animals↗
PubMedDate not supplied

Theophylline-induced changes in the mouse brainstem auditory evoked potential.

Because theophylline is a widely used analeptic, there is interest in its possible ototoxic and neurotoxic effects. The present study used the brainstem auditory evoked potential (BAEP) to evaluate the acute effects of theophylline on auditory electrophysiology in mice. Adult female C57BL/6 mice were injected intraperitoneally with 150 mg/kg theophylline or saline. The BAEP thresholds and latency-intensity profiles suggested that theophylline induced a rather slight but statistically significant change in auditory function that was suggestive of a temporary recruitment-type sensorineural deficit. This observation raises concerns about the possible ototoxic effects of theophylline, particularly in asthmatic patients and apneic preterm neonates who receive this drug chronically. While there was BAEP evidence of ototoxic effects for theophylline, there was no evidence of neurotoxic effects.

Animals↗
PubMedDate not supplied

The interactive effects of alcohol and cocaine on maternal and fetal toxicity in the Long-Evans rat.

The number of obstetric patients with polydrug abuse problems has increased substantially in recent years. One of the most common drug combinations is alcohol and cocaine. The effect of this drug combination on pregnancy is, therefore, of interest. Consequently, the present study investigated the relative and interactive effects of these two drugs on pregnancy outcome in an animal model. Alcohol and cocaine were administered, both separately and in combination, to separate groups of pregnant Long-Evans rats from gestation day 7-19. Animals were then sacrificed and examined on gestation day 20. Control animals were given vehicle only or were nontreated. The isobolographic method was used to evaluate the effects of the alcohol-by-cocaine interaction on select maternal and fetal variables. This method of analysis indicated that alcohol and cocaine had interactive effects that were linearly additive for some variables and infraadditive for others. In general, the results suggest that the alcohol-plus-cocaine drug combination poses a greater risk to pregnancy than either drug alone.

Animals↗
PubMedDate not supplied

Dose-dependent consequences of cocaine on pregnancy outcome in the Long-Evans rat.

The number of obstetric patients abusing cocaine has increased dramatically in recent years. To better understand its effect on pregnancy and to establish the LD50s for maternal and fetal fatalities, the dose-dependent effects of cocaine on pregnancy outcome were investigated in the Long-Evans rat. Pregnant animals were given either saline or 40, 50, 60, 70, 80, or 90 mg/kg cocaine hydrochloride from gestation days 7 to 19 inclusive. An additional group was non-treated and had ad lib access to food and water. Animals were sacrificed on gestation day 20 and the fetuses were examined. Despite treatment during the major periods of organogenesis and brain development, few congenital abnormalities were observed. There were, however, dose-dependent effects on maternal weight gain, maternal food and water consumption, fetal weight, maternal and fetal fatalities, fetal edema, abruptio placentae and cephalic hemorrhages. Despite suppression of maternal weight gain, there was preservation of fetal weights at cocaine doses up to and including 80 mg/kg/day, suggesting some protection of fetal growth. In addition to providing information on the gestational effects of cocaine in the rat, the present study provides information useful in guiding the selection of cocaine doses for subsequent behavioral teratology studies.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Prenatal cocaine exposure in the Long-Evans rat: I. Dose-dependent effects on gestation, mortality, and postnatal maturation.

Pregnant Long-Evans rats were injected daily with 40, 60, 80, or 100 mg/kg cocaine HCl (SC, 2% solution) from gestational days 7-20 (sperm positive = day 0). Daily doses were split evenly with half given between 9:00-10:00 a.m. and half between 3:00-4:00 p.m. An ad lib-fed group as well as nutritional control groups that were pair-fed to the 80 and 100 mg/kg cocaine dams were also evaluated (N = 11-18 liters/group). Cocaine had no effect on gestational length but did cause dose-dependent decreases in maternal food consumption and weight gain and increases in maternal mortality. Interestingly, cocaine-treated dams shows a significant increase in water consumption. In terms of offspring variables, there was a dose-dependent decrease in birth weight and postnatal weight gain in both the cocaine and pair-fed groups. There were also dose-dependent effects on litter size, stillbirths and postnatal mortality in the cocaine-treated groups as compared to the control groups. High dose cocaine treatment caused delays in several indices of physical maturation (pinna detachment, fur growth, ear opening, eye opening, vaginal opening) but not in others (incisor eruption, testicular descent). Physical anomalies and postnatal morbidity, while uncommon, were observed in animals prenatally exposed to the higher cocaine doses. Collectively, these data suggest that prenatal cocaine exposure can increase postnatal morbidity as well as increase pre-and postnatal mortality in animal offspring.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Prenatal cocaine exposure in the Long-Evans rat: II. Dose-dependent effects on offspring behavior.

Pregnant Long-Evans rats were injected daily with 40, 60, 80 or 100 mg/kg cocaine HCl (SC, 2% solution) from gestational days 7-20 (sperm positive = day 0). Daily doses were split with half given between 9:00-10:00 a.m. and half between 3:00-4:00 p.m. An ad lib-fed group as well as nutritional control groups that were pair-fed to the 80 and 100 mg/kg cocaine dams were also evaluated (N = 11-18 litters/group). The negative geotactic reaction of the offspring, evaluated from day 2-14 (birth = day 0), showed no group differences. Spontaneous alternation behavior in a T-maze showed no evidence of perseveration in any group on either day 21 or day 80. Most cocaine-treated offspring showed an altered preference in turning right versus left on day 21. Activity monitor behavior showed that the cocaine-treated and pair-fed offspring were hypoactive on day 20. Some degree of hypoactivity was still evident on day 49, but absent on day 80. The passive avoidance behavior of day 19 offspring showed no group differences in acquisition of task learning. The 100 mg/kg cocaine offspring did show significantly poorer retention of task learning 48 hr later. On day 80, no group differences were seen in passive avoidance behavior. Acquisition of an active avoidance behavior on day 80 was significantly poorer in the 100 mg/kg cocaine group.

Animals↗
PubMedDate not supplied

Prenatal cocaine exposure in the Long-Evans rat: III. Developmental effects on the brainstem auditory-evoked potential.

Prenatal cocaine exposure has been associated with a variety of adverse neurological effects in infants and laboratory animals. Of particular interest, one group of investigators reported that exposed neonates have an abnormality in the brainstem auditory-evoked potential (BAEP). The particular abnormality, a prolongation in the wave I-V interpeak latency, suggested delayed or desynchronized transmission of subcortical auditory information. To further investigate this possible consequence of prenatal cocaine exposure, pregnant Long-Evans rats were injected daily with 60, 80 or 100 mg/kg cocaine HCl (SC, 2% solution) with half the daily dose given in the morning and the other half given in the afternoon. Treatment was given from gestation days 7 to 20 (sperm positive = GD 0). Ad lib-fed and pair-fed control groups were also used. Offspring were evaluated at the age of 35 days (birth = PD 0) and as adults (6-10 months). BAEPs were elicited by click stimuli presented over a broad range of intensities and repetition rates. Prolongation of the interpeak latencies and a reduction in BAEP amplitudes were observed only in the highest dose (C100) group, only at the age of 35 days, and only at the highest stimulus intensity. While these results support those found in exposed neonates, our data suggest a) that the effects are developmental delays which dissipate with aging and b) that the effects require high cocaine exposure.

Acoustic Stimulation↗
PubMedDate not supplied

Interactive effects of prenatal alcohol and cocaine exposures on postnatal mortality, development and behavior in the Long-Evans rat.

Polydrug abuse has increased substantially in recent years amongst obstetric patients. One of the most common drug combinations is alcohol and cocaine. To better understand the adverse consequences of this drug combination on pregnancy and the offspring, alcohol (2 g/kg, b.i.d.) and cocaine HCl (30 mg/kg, b.i.d.) were administered individually and in combination to separate groups of pregnant Long-Evans rats from gestation days 7-20. The pregnant dams were evaluated for maternal weight gain, food and water consumption, mortality, and gestational length. The offspring were evaluated for physical maturation, mortality, and behavior. The drug combination was found to have greater effects regarding decreased birth weight, increased postnatal mortality, and delayed physical maturation than either drug alone. Drug treatments also influenced activity monitor behavior in that prenatal cocaine exposure was associated with hypoactivity while the alcohol and the alcohol-plus-cocaine treatments were associated with hyperactivity in periweanling pups. Drug treatments had no significant effects on passive or active avoidance behaviors. These results suggest that combining alcohol and cocaine increases the risk to the offspring.

Animals↗
PubMedDate not supplied

Prenatal cocaine exposure in the laboratory mouse: effects on maternal water consumption and offspring outcome.

Pregnant mice were given 50 mg/kg cocaine HCl (1% solution, sc) once daily from gestation days 7 through 18 (sperm positive = day 0; term = day 19). Pair-fed and untreated control groups were also used. The pregnant cocaine-treated females showed normal weight gain and food consumption but had significantly increased water consumption. The cocaine-treated group had a significant increase in embryonic resorptions but no significant effects on stillbirths or postnatal mortality. The offspring of cocaine-treated females had significantly reduced birth weights and postnatal weight gains up to the age of 28 days. There was also a delay in their ear opening but not in other maturational milestones. Increased water consumption following cocaine treatment has been reported by other studies. We speculate that cocaine has a diuretic effect. We discuss the implications of this effect during pregnancy.

Analysis of Variance↗
PubMedDate not supplied

Prenatal cocaine and alcohol exposures affect rat behavior in a stress test (the Porsolt swim test).

Prenatal cocaine and alcohol exposures have been associated with a variety of adverse effects ranging from subtle neurobehavioral abnormalities to major malformations. In this study, we used the Porsolt swim test to assess the effects of prenatal cocaine and alcohol exposures on stress-related behavior. Pregnant Long-Evans rats were injected daily with 80 mg/kg cocaine HCl (SC) or 6.2-6.5 g/kg ethyl alcohol (PO) from gestation days 7-20 with half the dose given in the morning and the other half in the afternoon. Pair-fed and ad lib control groups were also used. One male offspring from each litter was evaluated in the Porsolt swim test at the age of 120 days. The alcohol and cocaine groups were less immobile (i.e., struggled more to escape) than the controls. These results suggest that prenatal exposure to either alcohol or cocaine can adversely affect behavior in stressful or fearful situations.

Animals↗
PubMedDate not supplied

Comparative effects of prenatal cocaine, alcohol, and undernutrition on maternal/fetal toxicity and fetal body composition in the Sprague-Dawley rat with observations on strain-dependent differences.

Pregnant rats received either 20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7 through 19. Pair-fed and untreated control groups and a group receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups. Females were sacrificed on gestation day 20 and the fetuses examined. Maternal weight gain and food consumption showed dose-dependent decreases. Maternal water consumption, by contrast, was significantly increased in the cocaine-treated animals and may reflect a diuretic effect. The maternal mortality rates in Sprague-Dawley rats were less than in two strains of Long-Evans rats, suggesting important strain-dependent differences in susceptibility to cocaine toxicity. Cocaine caused a significant dose-dependent decrease in fetal weights. Physical anomalies in the cocaine-exposed and alcohol-exposed fetuses included occasional hemorrhaging, edema, anophthalmia, and limb reduction. Despite increased maternal water consumption by cocaine-treated dams, there were no increases in fetal body water content. There were, however, significant decreases in fetal body fat content in the pair-fed, alcohol-treated, and two highest cocaine-treated groups.

Analysis of Variance↗
PubMedDate not supplied

Cisplatin-induced increases in spontaneous neural activity in the dorsal cochlear nucleus and associated outer hair cell loss.

Tinnitus is one of the consequences of cisplatin chemotherapy, but its underlying mechanisms are not well understood. Since it has been shown that cisplatin causes outer hair cell loss, it is possible that loss of these cells might induce tinnitus by increasing spontaneous activity in the central auditory system. To test this possibility, the present study examined the effects of cisplatin treatment on cochlear hair cells and on spontaneous neural activity in the dorsal cochlear nucleus of hamsters. Recordings, carried out approximately 1 month after cisplatin treatment, demonstrated significant increases in spontaneous activity across broad regions of the dorsal cochlear nucleus relative to levels in saline-treated controls. Histological results showed that cisplatin-treated animals also displayed dramatic loss of outer hair cells over most of the basal turn of the cochlea. Inner hair cells remained intact, although some evidence of damage to their stereocilia was evident. These findings indicate that cisplatin treatment causes abnormalities in spontaneous activity in the dorsal cochlear nucleus that are associated with widespread damage to outer hair cells. However, since some damage to inner hair cells was also observed, the role of inner hair cell injury in contributing to higher spontaneous activity cannot be ruled out.

Animals↗