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G Elmer

Publications and source records attributed to G Elmer.

10 recordsLinked to original sources

Rats and mice share common ethologically relevant parameters of exploratory behavior.

Detailed studies of rat exploratory behavior reveal that it consists of typical behavior patterns having a distinct structure. Recently we have developed interactive software that uses as input the automatically digitized time-series of the animal's location for the visualization, analysis, capturing and quantification of these patterns. We use this software here for the study of BALB/cJtau mouse behavior. The results suggest that a considerable number of rat patterns are also present in the mouse. These ethologically-relevant patterns have a significant potential as a phenotyping tool.

Algorithms↗

Controlling the false discovery rate in behavior genetics research.

The screening of many endpoints when comparing groups from different strains, searching for some statistically significant difference, raises the multiple comparisons problem in its most severe form. Using the 0.05 level to decide which of the many endpoints' differences are statistically significant, the probability of finding a difference to be significant even though it is not real increases far beyond 0.05. The traditional approach to this problem has been to control the probability of making even one such error--the Bonferroni procedure being the most familiar procedure achieving such control. However, the incurred loss of power stemming from such control led many practitioners to neglect multiplicity control altogether. The False Discovery Rate (FDR), suggested by Benjamini and Hochberg [J Royal Stat Soc Ser B 57 (1995) 289], is a new, different, and compromising point of view regarding the error in multiple comparisons. The FDR is the expected proportion of false discoveries among the discoveries, and controlling the FDR goes a long way towards controlling the increased error from multiplicity while losing less in the ability to discover real differences. In this paper we demonstrate the problem in two studies: the study of exploratory behavior [Behav Brain Res (2001)], and the study of the interaction of strain differences with laboratory environment [Science 284 (1999) 1670]. We explain the FDR criterion, and present two simple procedures that control the FDR. We demonstrate their increased power when used in the above two studies.

Animals↗

Natural segmentation of the locomotor behavior of drug-induced rats in a photobeam cage.

Recently, Drai et al. (J Neurosci Methods 96 (2000) 119) have introduced an algorithm that segments rodent locomotor behavior into natural units of 'staying in place' (lingering) behavior versus going between places (progression segments). This categorization, based on the maximum speed attained within the segment, was shown to be intrinsic to the data, using the statistical method of Gaussian Mixture Model. These results were obtained in normal rats and mice using very large (650 or 320 cm) circular arenas and a video tracking system. In the present study, we reproduce these results with amphetamine, phencyclidine and saline injected rats, using data measured by a standard photobeam tracking system in square 45 cm cages. An intrinsic distinction between two or three 'gears' could be shown in all animals. The spatial distribution of these gears indicates that, as in the large arena behavior, they correspond to the difference between 'staying in place' behavior and 'going between places'. The robustness of this segmentation over arena size, different measurement system and dose of two psychostimulant drugs indicates that this is an intrinsic, natural segmentation of rodent locomotor behavior. Analysis of photobeam data that is based on this segmentation has thus a potential use in psychopharmacology research.

Algorithms↗

Mu opiate receptor gene dose effects on different morphine actions: evidence for differential in vivo mu receptor reserve.

Homozygous transgenic knockout mice without mu-opioid receptors lack morphine-induced antinociception, locomotion, tolerance, physical dependence, and reward. mu receptors thus appear to play central roles in these morphine actions. Different levels of mu receptor expression are found in different humans and in different animal strains. In vitro studies indicate that some morphine responses persist after inactivation of as many as 90% of the initial mu receptor complement, while others are attenuated after inactivating many fewer receptors. Varying levels of mu receptor reserve could thus exist in different mu-expressing neuronal populations in vivo. Heterozygous mu receptor knockout mice express half of wild-type mu receptor levels. Tests of morphine actions in these mice reveal evidence for differing mu receptor reserves in brain circuits that mediate distinct opiate effects. Heterozygotes display attenuated locomotion, reduced morphine self-administration, intact tolerance, rightward shifts in morphine lethality dose/effect relationships, and variable effects on place preference compared to wild-type mice. They demonstrate full physical dependence, as measured by naloxone-precipitated abstinence following five days of morphine administration. Neuroadaptive changes in sites other than mu receptors could be involved in some of these results. Nevertheless, these data document substantial influences that individual differences in levels of mu receptor expression could exert on distinct opiate drug effects. They support the idea that functional mu receptor reserve differs among the diverse neuronal populations that mediate distinct properties of opiate drugs.

Animals↗

Lack of involvement of delta-opioid receptors in mediating the rewarding effects of cocaine.

The non-selective opioid antagonist naltrexone and the partial agonist buprenorphine have been reported to reduce cocaine self-administration (SA) and relapse in both humans and rhesus monkeys. Data suggesting an involvement of delta-opioid receptors in modulating the conditioned rewarding effects of cocaine were also recently presented. In view of such findings, the present SA and place conditioning studies were conducted to examine the influence of the selective delta-opioid receptor antagonist naltrindole upon the rewarding effects of cocaine. Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg per infusion) on an FR2 schedule of reinforcement. Dose-response and antagonist testing commenced once stable rates of cocaine SA were achieved. For antagonist testing, rats received naltrindole (0.03-10.0 mg/kg, IP) 30 min prior to the start of 2-h SA sessions. SA behavior in response to cocaine delivery (0.25 and 1.0 mg/kg per infusion) was then determined. Naltrindole in doses of 0.03-3.0 mg/kg did not alter the number of cocaine infusions taken by the rats. A higher dose of naltrindole (10.0 mg/kg), which markedly depressed locomotor activity, resulted in a 16% reduction of cocaine (0.25 mg/kg per infusion) SA behavior. When SA sessions were terminated and naltrindole (1.0 mg/kg) was administered repeatedly for 3 days, no alterations in the re-acquisition of cocaine SA were seen. Place conditioning studies also failed to find an effect of naltrindole (0.1-3.0 mg/kg) on cocaine (10 mg/kg)-induced conditioned place preferences. Naltrindole, by itself, did not induce significant place conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii.

Recurrence of Clostridium difficile-associated diarrhea and pseudomembranous colitis occurs in up to 20% of patients after standard therapy. In these patients, subsequent recurrences are even more frequent. Saccharomyces boulardii, a nonpathogenic yeast, was found to be effective in preventing clindamycin cecitis recurrence in an animal model. We performed an open trial of S. boulardii to evaluate its efficacy in treating recurrences of C. difficile-associated colitis in humans. Thirteen patients with recurring C. difficile cytotoxin-positive diarrhea (who had an average of 3.6 previous recurrences) were treated with 10 days of vancomycin and a 30-day course of S. boulardii. Eleven (85%) had no further recurrences. S. boulardii may have a role in treating recurrent C. difficile diarrhea and colitis.

Antidiarrheals↗