Acquisition and loss of behaviorally augmented tolerance to ethanol in the rat

Abstract

The phenomenon of behavioral augmentation of tolerance (BAT) to ethanol (EtOH) in the rat was replicated in studies using the moving belt test of intoxication. Rats performing the test daily under the influence of EtOH (2.2 or 2.5 g/kg i.p.) developed tolerance more rapidly than those receiving the same dose after each daily session on the belt. However, both groups reached the same maximum level of tolerance. Acceleration of tolerance by BAT was proportional to the frequency of performance under the influence of EtOH when total exposure to EtOH was held constant. The degree of tolerance produced by BAT could not be increased by daily gavage with a large dose (6 g/kg) of EtOH. After termination of EtOH administration, tolerance produced by BAT was lost at the same rate, whether or not daily alcohol-free sessions on the belt test were given. These findings are consistent with the hypothesis that BAT and conventionally produced tolerance differ only in rate.

Effects of Ethanol on Multiple Fixed‐interval Fixed‐ratio Schedule Performances: Dynamic Interactions at Different Fixed‐ratio Values

“…Though chronic (daily) drug administration is not essential for tolerance to occur, it is significant that shifts in the doseeffect curves did not occur during the ascending series. Although pharmacological accounts of tolerance do not appear applicable to the present findings (see e.g., LeBlanc, Kalant, Gibbins, & Berman, 1969), there are a number of studies indicating that tolerance-like plienomena can emerge by enivironmental or nonpharmacological manipulations (e.g., LeBlanc & Cappell, 1977;Schuster, Dockens, k Woods, 1966;Siegel, 1975; see review by Corfield-Sumner & Stolerman, 1978). Both the shifts to the right in the dose-effect curve and the increased effects obtained with ethanol upon re-exposure to the lower FR values would appear to be more directly attributable to residual but enduring effects produced by the behavioral experience and drug effects under the higher-valued FR schedules.…”

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

“…Furthering the notion that NAC Homer2b overexpression elicits a behavioral phenotype similar to that produced by repeated alcohol experience (eg Crabbe et al, 1981Crabbe et al, , 1982Kalant et al, 1978;LeBlanc et al, 1969;Phillips et al, 1991;Tabakoff and Culp, 1984;Tabakoff et al, 1980), tolerance developed to alcohol's motor-impairing effects following the repeated administration of a moderate dose of alcohol only in mice overexpressing Homer2b (Figure 4). While increases and decreases, respectively in NAC Homer2b overexpression appear to be sufficient to promote and prevent tolerance to alcohol's motor-impairing effects (Szumlinski et al, 2005b;Figure 4), recent evidence implicates both mGluR1 and NMDA receptors in regulating alcohol-induced sedation and motor sensitization (eg Kotlinska et al, 2006;Lominac et al, 2006).…”

Evidence-based treatments of addiction

“…If drug taking does not resume, homeostatic mechanisms will gradually readapt to the absence of the drug (LeBlanc et al 1969) and tolerance will be diminished or lost. We now know that detoxification is, at best, a first step in treatment and that simply achieving a drug-free state is not the most significant accomplishment.…”