Withdrawal from an acute bolus injection of ethanol produces affective or emotional signs that include anxiogenic-like behavior and conditioned place aversion. This study assessed whether brain reward deficits that accompany withdrawal from chronic ethanol dependence are also observed upon withdrawal from acute intoxication. Rats were implanted with stimulating electrodes aimed at the medial forebrain bundle in the lateral hypothalamus and trained on a discrete-trial current-intensity brain stimulation reward threshold paradigm. Ethanol intoxication was produced by bolus intraperitoneal injections of ethanol (1.0, 1.5, or 2.0 g/kg). Brain reward thresholds were monitored periodically following the bolus injection (3, 6, 9, 12, 24, 48, 72, 96 h postethanol). Blood samples taken at various intervals postethanol revealed that peak blood alcohol levels (BAL) at all doses tested were reached within 10 min of injection. Following doses of 1.0, 1.5, and 2.0 g/kg ethanol, BAL had declined to undetectable levels within 3-6 h postinjection. Withdrawal from a single injection of ethanol resulted in a significant but transient increase in brain reward thresholds only with the highest ethanol dose tested (2.0 g/kg). When acute intoxication and withdrawal episodes were repeated two additional times at weekly intervals, the peak magnitude and duration of threshold elevation increased significantly at the 2.0 g/kg dose of ethanol. A significant but transient increase in thresholds was also seen in the group treated with 1.5 g/kg ethanol during the third and final week of testing. Results indicate that withdrawal from a single exposure to an intoxicating dose of ethanol produces significant brain reward deficits in addition to other affective disturbances previously reported, and that repeated weekly intoxication and withdrawal results in a progressive increase in magnitude and duration of the reward deficit. (c) 2006 Elsevier Inc. All rights reserved.