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Biomedical subjects

M M Ford

Publications and source records attributed to M M Ford.

6 recordsLinked to original sources
PubMed2007

Mouse inbred strain differences in ethanol drinking to intoxication.

Recently, we described a simple procedure, Drinking in the Dark (DID), in which C57BL/6J mice self-administer ethanol to a blood ethanol concentration (BEC) above 1 mg/ml. The test consists of replacing the water with 20% ethanol in the home cage for 4 h early during the dark phase of the light/dark cycle. Three experiments were conducted to explore this high ethanol drinking model further. In experiment 1, a microanalysis of C57BL/6J behavior showed that the pattern of ethanol drinking was different from routine water intake. In experiment 2, drinking impaired performance of C57BL/6J on the accelerating rotarod and balance beam. In experiment 3, 12 inbred strains were screened to estimate genetic influences on DID and correlations with other traits. Large, reliable differences in intake and BEC were detected among the strains, with C57BL/6J showing the highest values. Strain means were positively correlated with intake and BEC in the standard (24 h) and a limited (4 h) two-bottle ethanol vs. water test, but BECs reached higher levels for DID. Strain mean correlations with other traits in the Mouse Phenome Project database supported previously reported genetic relationships of high ethanol drinking with low chronic ethanol withdrawal severity and low ethanol-conditioned taste aversion. We extend these findings by showing that the correlation estimates remain relatively unchanged even after correcting for phylogenetic relatedness among the strains, thus relaxing the assumption that the strain means are statistically independent. We discuss applications of the model for finding genes that predispose pharmacologically significant drinking in mice.

Alcohol Drinking↗
PubMed2004

Sex differences in the effect of ethanol injection and consumption on brain allopregnanolone levels in C57BL/6 mice.

The pharmacological profile of allopregnanolone, a neuroactive steroid that is a potent positive modulator of gamma-aminobutyric acidA (GABAA) receptors, is similar to that of ethanol. Recent findings indicate that acute injection of ethanol increased endogenous allopregnanolone to pharmacologically relevant concentrations in male rats. However, there are no comparable data in mice, nor has the effect of ethanol drinking on endogenous allopregnanolone levels been investigated. Therefore, the present studies measured the effect of ethanol drinking and injection on allopregnanolone levels in male and female C57BL/6 mice. One group was given 17 days of 2-h limited access to a 10% v/v ethanol solution in a preference-drinking paradigm, while another group had access to water only. The ethanol dose consumed in 2 h exceeded 2 g/kg. Then, separate groups of mice were injected with either 2 g/kg ethanol or saline. Mice were killed 30 min after the 2-h drinking session or injection. Blood ethanol concentration was significantly higher in the ethanol-injected versus ethanol-drinking groups, even though the dose was similar. Consumption of ethanol significantly increased brain allopregnanolone levels in male but not female mice, compared with animals drinking water, but did not alter plasma corticosterone levels. In contrast, injection of ethanol did not significantly alter brain allopregnanolone levels in male or female mice and only significantly increased plasma corticosterone levels in the male mice, when compared with saline-injected animals. The sex differences in the effect of ethanol administration on endogenous allopregnanolone levels suggest that the hormonal milieu may impact ethanol's effect on GABAergic neurosteroids. Importantly, these data are the first to report the effect of ethanol drinking on allopregnanolone levels and indicate that ethanol consumption and ethanol injection can produce physiologically relevant allopregnanolone levels in male mice. These results have important implications for studies investigating the potential role of endogenous allopregnanolone levels in modulating susceptibility to ethanol abuse.

Alcohol Drinking↗
PubMed1999

Pulsatile output of prostaglandin F(2alpha) does not increase around the time of luteolysis in the pregnant goat.

Prostaglandin (PG) F(2alpha) secreted from the uterus is the luteolysin of the estrous cycle and is also believed to be responsible for luteolysis in the pregnant doe at term. We have reported that basal progesterone concentrations decrease before basal PGF(2alpha) concentrations increase, which is inconsistent with this view. In this study we investigated whether luteolysis is associated with increased frequency or amplitude of pulsatile PGF(2alpha) secretion in does over the last 2 wk of gestation. Progesterone concentrations decreased approximately 1 wk before parturition. There was no accompanying increase in PGF(2alpha) concentrations or pulse frequency, and those pulses that were observed were of lesser amplitude and duration than those that have been associated with luteolysis in cycling ewes. A small increase in PGF(2alpha) pulse frequency was identified during the 3 days before parturition, but this was not associated with any change in progesterone concentrations. The biological significance of these small changes in PGF(2alpha) pulse frequency is obscure, although the high concentration of this eicosanoid at labor may have been related to the final, precipitous decline in plasma progesterone concentrations. These findings do not support the notion that PGF(2alpha) is the principal luteolysin in the pregnant doe at term.

Animals↗
PubMed1998

Fetal and maternal endocrine changes approaching parturition in the goat: lack of evidence for prostaglandins E2 and F2alpha as signals for luteolysis.

We investigated the temporal relationship of fetal cortisol secretion to circulating concentrations of fetal ACTH1-39 and its high-molecular weight precursors in goats. We also measured the concentrations of progesterone, estradiol-17beta estrone sulfate, prostaglandin (PG) E, PGF2alpha, and PGF2alpha metabolite (PGFM) in maternal arterial plasma over the last month of gestation. Prostaglandin concentrations were also measured in utero-ovarian venous plasma. There was a positive association between ACTH1-39 in fetal plasma and the prepartum surge in fetal cortisol that commenced 8 days before labor. The fetal cortisol surge was followed by a simultaneous decrease in maternal progesterone and an increase in plasma estrogens commencing 3-4 days before labor. No change in basal prostaglandin concentration occurred before this time. There was a positive veno-arterial difference of PGE and PGF2alpha across the uterine vascular bed, confirming the uteroplacental unit as a major source of these eicosanoids in the plasma of the pregnant doe. We conclude that the fetal signal for parturition precedes luteolysis by some 5 days and find no evidence of changes in the basal concentrations of PGE and PGF2alpha in maternal plasma at the time of luteolysis.

Adrenocorticotropic Hormone↗
PubMed1977

46,XX/47XX, + 14 mosaicism in a liveborn infant.

A liveborn infant with the complement 46,XX/47,XX, + 14 shared certain features in common with the following previously reported cases: (1) the one previously reported possible case of trisomy 14, (2) cases in which individuals had at least some portion of chromosome No. 14 in triplicate, and (3) cases of atypical D trisomy (Snodgrass category II). The common features include developmental retardation, wide flat nose with bulbous or wide tip, large mouth with turned down corners (some with protruding lips), short neck (some with redundant skin folds), low-set ears, retrognathia, digital anomalies (usually contractions and deviations), palatal anomalies, and cryptorchidism.

Child Development↗