ArticlesEffect of Lipid Solubility on the Development of Chronic Cross-Tolerance Between Ethanol and Different Alcohols and Barbiturates
Section snippets
Animals
Male Sprague–Dawley rats weighing 150–200 g were obtained from Charles River Laboratories (Montreal, Quebec). They were housed singly and fed a standard laboratory rat chow in a daily ration which was individually adjusted to bring them all to a body weight of 250–280 g before any training or testing was carried out. Thereafter, each animal received five standard pellets daily for the balance of this study. Tap water was available at all times. The temperature of the colony room was maintained
Preliminary Dose-Response Studies
Groups of well-trained rats were used for preliminary log-dose response studies of various alcohols and barbiturates on the accelerod test. Each group was divided, on the basis of their initial scores, into four or five balanced subgroups. Each subgroup ( n = 5 or 6) received an assigned dose of the drug to be tested. The rats were then tested on the accelerod at 2.5, 7.5, 12.5 and 17.5 min after drug injection. Dose-response curves for the drugs examined in this way are shown in Fig. 1. The
Preliminary Dose-Response Studies
As shown in Fig. 1, the dose-response curves for the four alcohols (ethanol, n-propanol, n-butanol, t-butanol) and four barbiturates (barbital, phenobarbital, pentobarbital and thiopental) studies in detail were essentially parallel. It was therefore possible to estimate, by simple interpolation in the respective dose-response graphs, the dose of each drug that would produce a 60% impairment response (ED60). The ED60 was found to be inversely related to the octanol/water partition coefficient
Discussion
The results of this work indicate that chronic treatment with ethanol resulted in tolerance to ethanol on three different tests. The degree of tolerance to ethanol was roughly comparable in the three tests, but animals in the rotarod test took longer to develop tolerance than those in the other two tests. Since we used different batches of animals for different studies, we cannot tell whether the difference in time required to produce comparable levels of tolerance is due to differences between
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Benzyl alcohol increases voluntary ethanol drinking in rats
2014, Pharmacology Biochemistry and BehaviorCitation Excerpt :The present finding of longer lasting high frequencies of ethanol-mediated testosterone elevations in the high-drinking AA compared with low-drinking Wistar rats support our previous hypotheses about the role of testosterone in promoting ethanol drinking. BA is known to cause cross-tolerance to other alcohols, as e.g. ethanol (Khanna et al., 1997). On the other hand, tolerance has in several studies with experimental animals (McBride and Li, 1998) and with humans (Schuckit, 1994) been linked to the propensity to consume more ethanol.
Improved transformation of morphometric measurements for a priori parameter estimation in a physiologically-based pharmacokinetic model of ethanol
2007, Biomedical Signal Processing and ControlCitation Excerpt :As suggested, an unconstrained optimization does not mandate that VP (the “peripheral” volume) be larger than VB (the “blood” volume) or even positive, an obvious physiological constraint. Further, as the estimated volume of distribution for alcohol is approximately equal to the entire total body water [36–38,57], the sum of VP and VB was constrained to be less than 120% of TBW, allowing for error in that estimation and the influence of weak perfusion of alcohol into body fat [40,57]. Additionally, the diffusion constant kAT was held to be within the bounds of [0 1], mandating that this process must occur (non-zero), and is neither instantaneous and not facilitated (less than unity).
Selection for pentobarbital withdrawal severity: Correlated differences in withdrawal from other sedative drugs
2004, Brain ResearchCitation Excerpt :Preclinically, the development of tolerance to a given sedative agent can confer cross-tolerance to other sedatives (see Ref. [16]). However, cross-tolerance does not necessarily extend among all classes of sedative drugs or members of a given class of sedatives [16–18,20]. These findings suggest that even though physical dependence displays certain similarities across sedatives, some differences in the mechanisms of tolerance and/or dependence specific to each drug or type of drug may exist.
Importance of magnesium ions in development of tolerance to ethanol: Studies on cultured cerebral vascular smooth muscle cells, type-2 astrocytes and intact rat brain
2001, Brain Research BulletinCitation Excerpt :There is a decrease in the intoxicating effects of ethanol and a requirement for greater amounts of ethanol intake to achieve the near-identical intoxicating effects seen with acute initial ethanol administration. Such adaptation effects of ethanol are thought to be brought about via effects on cell membranes, lipid ordering, ligand-gated ion channels, voltage-gated calcium channels, diverse cell signaling pathways, and subcellular elements (see reviews [13,14,17,19,20,23,25,29,53]). Among signal transduction pathways, PKC, Ca2+ influx/release, and NMDA and GABAA receptors are the most sensitive to ethanol, and are clearly involved in the mechanisms that underlie tolerance to ethanol in the brain (see reviews [14,17,19,20,23,25,53]).