Factors involved in the differential response to ethanol, barbital and pentobarbital in rats selectively bred for ethanol sensitivity

Abstract

Two lines of rats, 'least affected' (LA) and 'most affected' (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested.

Differential pharmacological responses to ethanol, pentobarbital and morphine in rats selectively bred for ethanol sensitivity

“…2). This agrees well with previous reports of a lack of differential effects with respect to barbiturate-induced narcosis and motor impairment, and the observation of a much lower rate of pentobarbital elimination from the blood of female rats (Lester et al 1977;Mayer et al 1982). No analgesia was produced by the dose of pentobarbital used in any of the animal groups (Fig.…”

“…Although blood ethanol levels were not determined in this study, previous work has shown that, in preceding generations (up to F23), the differential response to ethanol stems to a large extent from differences in CNS sensitivity of these animals (Lester et al 1977;Bass and Lester 1980;Mayer et al 1982). Differences in response to ethanol can therefore be generalized to include hypothermia.…”

Retrospective self-reports of sensitivity to the effects of alcohol: Trait-like stability and concomitant changes with alcohol involvement.

“…A related possibility is that levels of initial alcohol sensitivity determine the extent to which tolerance can be acquired. This idea has been tested extensively in rodent models, with studies generally finding that animals bred for low alcohol sensitivity are less susceptible to acquisition of tolerance than are animals bred for higher alcohol sensitivity (e.g., Khanna et al, 1985;Mayer et al, 1982Mayer et al, , 1983Riley & Lochry, 1977). Moreover, some evidence suggests alcohol-non-preferring rodent strains-which generally show higher alcohol sensitivity-become more sensitive to alcohol's sedative effects with repeated exposures, whereas alcohol-preferring rats become less sensitive (Kurtz et al, 1996).…”