Some scientists now believe that the development of tolerance to alcohol is an important process in the drinking careers of individuals who eventually develop alcohol abuse or dependence. After the initiation of alcohol use, the development of tolerance may modify the intoxicating effects of ethanol, which may in turn contribute to the escalation of alcohol use that characteristically accompanies the development of physical dependence or other alcohol- related health problems. Biochemical and physiological changes in the cellular components of organ systems, particularly the nervous system, are believed to underlie the development of tolerance. Biological changes that accompany advancing age may, accordingly, be expected to influence (or limit) the ability of laboratory animals or of man to develop or maintain tolerance. The proposed research seeks to examine the acquisition and loss of tolerance to ethanol as those processes are influenced by age in the laboratory rat. The use of the laboratory rat will minimize the influence of life-history or life style variable that are often present in human studies, while providing for a more adequate test of the influence of age-related biological changes on the responsiveness to ethanol. Rats of three age groups representative of the life span will be compared. The Fischer 344 rat will be used owing to the extensive amount of normative aging data now available on this strain. Animals will first be tested for their initial impairment and rate of recovery from single challenge doses of ethanol. Different measures of drug impairment (motor coordination, hypothermia, hypnosis) and tolerance will be used, as performance on these measures may be differentially affected by age. Careful attention will be paid to pharmacokinetic variables to distinguish between dispositional and functional tolerance. Different subclasses of tolerance (acute rapid, chronic) will be evaluated to examine the possibility that the processes underlying those types of tolerance is differentially influenced by aging. The proposed systematic investigation of the influence of age on alcohol tolerance will provide valuable information pertaining to the consequences of drug use over the life span. The data obtained will provide a basis for the design of future probes into the biochemical mechanisms underlying the age-related effects.
| York, J L; Chan, A W (1994) Absence of acute tolerance to ethanol hypnosis in F-344 and BN/BIRIJ rats. Alcohol 11:31-4 |
| York, J L (1994) Influence of self-titration on the relationship between ethanol dose and chronic tissue toxicities: theoretical considerations. Alcohol 11:219-23 |
| York, J L; Chan, A W (1994) Age effects on chronic tolerance to ethanol hypnosis and hypothermia. Pharmacol Biochem Behav 49:371-6 |
