Differential effects of single versus repeated minocycline administration-Lack of significant interaction with chronic alcohol history

Neuroimmune cytokines are increased with alcohol withdrawal and may mediate clinical responses associated with alcoholism. Because minocycline regulates the level of cytokines, it has been suggested as a therapeutic for disorders associated with alcohol. Male Wistar rats were exposed to chronic intermittent alcohol (CIA) comprising three 5-day cycles of ethanol liquid diet separated by 2 days of withdrawal. Rats were tested on social interaction, a measure of anxiety-like behavior, followed immediately by collection of amygdala tissue to measure CCL2 and TNFα or collection of the blood to measure corticosterone (CORT). One group received a single minocycline injection 3 h into the final CIA withdrawal and was tested 2 h later. A second group received injections during each of the three withdrawals and was similarly tested during the final acute withdrawal. A third group received a single injection at 23 h into withdrawal (extended withdrawal) and was tested 6 h later. Results showed that CIA withdrawal increased anxiety-like behavior. A single injection of minocycline during the final acute withdrawal increased anxiety-like behavior in rats that consumed liquid diet with or without alcohol, but this effect disappeared with repeated injections of minocycline. Differences in alcohol intake, blood alcohol level, and plasma CORT levels did not explain results. Only repeated injections of minocycline decreased TNFα mRNA levels in rats that consumed liquid diet with or without alcohol. When a single injection of minocycline was given during extended withdrawal, it decreased CCL2 mRNA levels, but did not reverse the elevation of CCL2 protein. These results suggest that minocycline has actions in brain and on behavior, but minocycline does not significantly impact these actions in relation to alcohol withdrawal.