Acute tolerance to rate-decreasing effects of single doses of ethanol.
Acute tolerance occurs when behavioral impairment is greater at a given blood ethanol concentration (BAC) on the ascending versus descending limb of the BAC-time curve following administration of a single dose of ethanol, however studies utilizing learned behaviors have not been widely reported. We assessed acute tolerance to single doses of ethanol in five Lewis rats responding under a fixed-ratio (FR8) schedule of food presentation. Response rates for food during 1-min components (ending 2, 4, 11, 18, 33, and 57 min after ethanol administration) were determined, and BAC was measured immediately after each component using a rat breathalyzer. Ethanol (0.4, 0.6, 0.8, and 1.2 g/kg, i.p.) produced dose-related decreases in responding for food that tended to recover over time for all but the highest dose tested. Similarly, dose-related increases in BAC were also observed. Using either an analysis that expressed impairment per unit BAC on the ascending limb versus the descending limb (by assessing the area under the curve (AUC) for behavior and BAC on each limb), the slope of the function that relates the behavioral effect to BAC (each expressed as percent maximum effect), or a variant of the Mellanby method (hysteresis), acute tolerance was observed following a dose of 0.4 g/kg ethanol. Though behavior appeared to recover on the descending limb following higher doses (especially 0.6 and 0.8 g/kg), acute tolerance to these doses was not present.
Ginsburg
Brett C
BC
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA. ginsburg@uthscsa.edu
Martinez
Gerardo
G
Friesenhahn
Gregory
G
Javors
Martin
M
Lamb
R J
RJ
D000428:Alcohol Drinking / Q000009:adverse effects / Q000523:psychology*; D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal / Q000187:drug effects; D001944:Breath Tests / Q000379:methods; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D051381:Rats; D012055:Reinforcement Schedule; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol