Quantitative trait loci for sensitivity to acute ethanol and ethanol consummatory behaviors in rats.

Individuals with a low initial response to alcohol (i.e., ethanol) are at greater risk of developing alcohol abuse or dependence later in life.

Short-term selection for acute ethanol tolerance and sensitization from an F2 population derived from the high and low alcohol-sensitive selectively bred rat lines.

Previous studies have identified quantitative trait loci (QTL) in the inbred high and low alcohol-sensitive rat (IHAS1 and ILAS1) strains. The original development of the strains involved selection for ethanol sensitivity based on duration of the loss of the righting reflex (LORR) after a standard dose of ethanol. This paper confirms some of these QTL using a short-term selection procedure based on the difference between the blood ethanol level at LORR and regain of the righting response.

Confirmation of quantitative trait loci for ethanol sensitivity and neurotensin receptor density in crosses derived from the inbred high and low alcohol sensitive selectively bred rat lines.

Rationale: Genetically influenced alcohol sensitivity is thought to be an important risk factor for the development of alcoholism. An effective first step for identifying genes that mediate variation in alcohol sensitivity is through quantitative trait loci (QTL) mapping in model organisms.

Objective: Fourteen provisional QTLs related to alcohol sensitivity were previously mapped in an F2 derived from the IHAS1 and ILAS1 rat lines.

CYP2E1 and catalase influence ethanol sensitivity in the central nervous system.

Objectives: Genetic factors are known to influence the sensitivity and tolerance to ethanol in humans and laboratory animals. Ethanol is metabolized to acetaldehyde mainly by the alcohol dehydrogenase pathway (ADHs) and, to a lesser extent, by microsomal oxidization (CYP2E1) and the catalase-H2O2 system.

Methods: In this study, we examined the role of CYP2E1 and catalase in ethanol metabolism and sensitivity, using transgenic knockout Cyp2e1(-/-) mice, acatalasemic (Cs/Cs) mice, double mutant Cyp2e1(-/-)/Cs/Cs mice and their respective wild-type counterparts 129/sv, C3H/HeJ, 129/sv X C3H/HeJ mice.

Formation of ethyl nitrite in vivo after ethanol administration.

The purpose of the current study was to ascertain whether ethyl nitrite could be detected in vitro from the reaction of ethanol with peroxynitrite, as well as after administration of ethanol to mice. Ethyl nitrite analyte was determined by using gas chromatography--mass spectrometry with headspace analysis with the use of a solid-phase microextraction device. Peroxynitrite was allowed to react with ethanol under a variety of conditions in vitro.

Quantitative trait loci mapping for ethanol sensitivity and neurotensin receptor density in an F2 intercross derived from inbred high and low alcohol sensitivity selectively bred rat lines.

Background: Genetic variance in initial sensitivity to ethanol has been implicated as a risk factor for the development of alcoholism. Identification of the genes that confer differential initial sensitivity is an important goal for the development of new treatment strategies and for a comprehensive understanding of the mechanism of ethanol's action. Quantitative trait loci (QTL) mapping for initial sensitivity and other ethanol-related behavioral traits in model organisms has become an important first step for the ultimate identification of genes that contribute to variation in ethanol responses.

Behavioral characterization of alcohol-tolerant and alcohol-nontolerant rat lines and an f(2) generation.

The Alcohol Tolerant (AT) and Alcohol Nontolerant (ANT) rats, selectively bred for ethanol-induced ataxia on the inclined plane at ALKO in Finland, were moved to the University of Colorado in 1998. The selection phenotype was tested on generation 60 animals in Colorado. In week one, ataxia was measured on the inclined plane 30 minutes after an intraperitoneal dose of 2 g/kg 15% w/v ethanol.

Short-term selection for the interaction between S-propranolol and ethanol in mice.

Background: We have previously demonstrated that there is an interaction between S-propranolol, a beta-adrenergic blocking agent, and ethanol on the hypnotic sensitivity of inbred short- and long-sleep mice (ISS and ILS). We found that the interaction was due to an additive hypothermic effect of ethanol and S-propranolol that markedly decreased the disappearance rate of ethanol. There was no discernible effect of S-propranolol on the hypnotic actions of ethanol as evidenced by the waking blood ethanol levels.

Interaction between S-propranolol and ethanol in mice selectively bred for ethanol sensitivity: the inbred short- and long-sleep mice.

Background: We have studied the effect of a beta-adrenergic blocking agent, S-propranolol, on the response of mice to anesthetic doses of ethanol. We used the selectively bred short and long sleep (ISS and ILS) mice. These mice were selected for their differential sensitivity to anesthetic doses of ethanol and then inbred.