Reduction in Ethanol Self-Selection of C57BL/6j Mice During Treatment with 3-((2-Imidazoline-2yl) Methyl) Indole

Abstract

Drugs which inhibit ethanol self-selection in animals (1) may also reduce intake of other preferred fluids such as saccharin solutions (2). Some drugs produce persistent rejection of ethanol after the drug is withdrawn (3, 4), suggesting a conditioned aversion perhaps due to a general toxic effect, a common Occurrence in rodents. At a low dose the title compound (shortened to "indole imidazoline") has been found to produce aversion to ethanol which promptly reverses upon withdrawal of the drug. Total fluid consumption is unaffected in a two choice situation, indicating that ethanol aversion is not a general toxic effect in this case.Materials and Methods. Twenty-five male mice of the C57BL/6j strain (Jackson Lab., Bar Harbour, ME) were used in the investigation because of their known high selfselection index for alcohol ( 5 ) . The animals were given a choice between distilled H20 and a 10% solution made from 95% ethanol and distilled H20. The substances were presented in 15 ml centrifuge tubes graduated in 0.1 ml increments. Readings were taken every 24 hr for 10 days predrug, 4 days during-drug treatment and 4 days postdrug. Every other day the position of the bottles was switched to control for position effects. Dluring drug treatment days, indole imidazoline as the tosylate salt was placed in both the water and 10% ethanol so that the mice would obtain 5 mg/kg/day of the salt based on a consumption level of 5 ml/day. These values were selected as optimal after pilot experiments.Blood levels of ethanol and acetaldehyde following intraperi toneal injection of ethanol an employee of The Dow Chemical Company.1This research was completed while C. W. S. was or ethanol plus indole imidazoline were obtained. Mice were injected intraperitoneally with a 10% solution of redistilled ethanol (1 g/kg) in physiological saline. Half the animals received 1 mg/kg indole imidazoline administered subcutaneously in the back immediately after injection of ethanol. A single solution of ethanol was prepared, sealed with a serum bottle cap, stored at 4O, and used for the entire experiment, Analytically, there was no change in concentration from beginning to end of the study.At appropriate times the mice were sac-T X