Rapid tolerance as an index of chronic tolerance

Khanna, J. M.; Kalant, H.; Shah, G.; Weiner, Jeff L.

doi:10.1016/0091-3057(91)90302-i

Cited by 67 publications

(27 citation statements)

References 6 publications

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“…Similarly, RTOL and CTOL to ethanol hypothermia were significantly correlated across 20 inbred strain means (data not shown, from Crabbe et al, 1982). Numerous studies show similarity of pharmacological responses of measures of RTOL and CTOL Morato, 2000, 2001;Kalant, 1996;Khanna et al, 1991Khanna et al, , 1994. However, in HRT and LRT mice, there was no effect of either MK-801 or D-cycloserine on RTOL (N.R.…”

Section: Discussionmentioning

confidence: 51%

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

et al. 2006

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Mice from eight inbred strains were studied for their acute sensitivity to ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction from pre-injection baseline of their body temperature. Two weeks later, mice were tested for their loss of righting reflex (LRR) after a higher dose of ethanol. The LRR was tested using the "classical" method of watching for recovery in animals placed on their backs in a V-shaped trough and recording duration of LRR. In a separate test, naive animals of the same strains were tested for HT repeatedly to assess the development of rapid (RTOL) and chronic tolerance (CTOL). We have recently developed a new method for testing LRR that leads to a substantial increase in the sensitivity of the test. Strains also have been found to differ in the new LRR test, as well as in the development of acute functional tolerance (AFT) to this response. In addition, our laboratory has periodically published strain difference data on the older versions of the HT and LRR responses. The earlier tests used some of the exact substrains tested currently, while for some strains, different substrains (usually, Nih versus Jax) were tested. We examined correlations of strain means to see whether patterns of strain differences were stable across time and across different test variants assessing the same behavioral construct. HT strain sensitivity scores were generally highly correlated across a 10-23 years period and test variants. The CTOL to HT was well-correlated across studies, and was also genetically similar to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this may be because different phenotypic end points were compared. The LRR data, which included a variant of the classical test, were not as stable. Measures of LRR onset were reasonably well correlated, as were those taken at recovery (e.g., duration). However, the two types of measures of LRR sensitivity to ethanol appear to be tapping traits that differ genetically. Also, the pattern of genetic correlation between HT and LRR initially reported in 1983 was not seen in current and contemporaneous studies. In certain instances, substrain seems to matter little, while in others, substrains differed a great deal. These data are generally encouraging about the stability of genetic differences.

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Section: Discussionmentioning

confidence: 51%

Effects of Genetic and Procedural Variation on Measurement of Alcohol Sensitivity in Mouse Inbred Strains

et al. 2006

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“…Because octopamine in invertebrates is thought to be functionally homologous to noradrenaline in vertebrates (reviewed in Evans, 1980;Roeder, 1999), these data demonstrate interesting similarities among the mechanisms of ethanol tolerance in flies and mammals. In addition, several quantitative aspects of tolerance, such as the extent of maximal tolerance and its duration (about 24 h), are also comparable in flies and rodents (Khanna et al, 1991(Khanna et al, , 1996. This opens the door for a genetic analysis of tolerance in Drosophila, an approach that will likely provide much needed molecular insight into the process in mammals, including humans.…”

Section: Ethanol Tolerance In Drosophilamentioning

confidence: 99%

Invertebrate models of drug abuse

2002

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Susceptibility to drug addiction depends on genetic and environmental factors and their complex interactions. Studies with mammalian models have identified molecular targets, neurochemical systems, and brain regions that mediate some of the addictive properties of abused drugs. Yet, our understanding of how the primary effects of drugs lead to addiction remains incomplete. Recently, researchers have turned to the invertebrate model systems Drosophila melanogaster and Caenorhabditis elegans to dissect the mechanisms by which abused drugs modulate behavior. Due to their sophisticated genetics, relatively simple anatomy, and their remarkable molecular similarity to mammals, these invertebrate models should provide useful insights into the mechanisms of drug action. Here we review recent behavioral and genetic studies in flies and worms on the effects of ethanol, cocaine, and nicotine, three of the most widely abused drugs in the world.

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“…Ethanol tolerance has been studied in different paradigms according to the period in which it develops: acute tolerance is observed during the course of a single ethanol administration, chronic tolerance is detected after several days, weeks, or months of repeated ethanol administrations, and rapid tolerance is detected between 8 and 24 h after the effects of the first ethanol administration vanish (Crabbe et al 1979;Khanna et al 1990Khanna et al , 1991Littleton et al 1980;Tabakoff 1995).…”

Section: Introductionmentioning

confidence: 98%