Changes in drinking behaviour and cholinergic binding sites induced by intermittent long-term ethanol treatment in the male rat.

Abstract

Male rats were treated with ethanol for approximately 1 year. One group of rats (Group 1) could, for 24 hr each week, choose between ethanol (10%, w/v) and water as drinking fluid. At the end of each choice period, 2.0 g/kg ethanol was given ip. A second group (Group 2) had the same choice as Group 1, but was given a saline injection. A third group (Group 3) could at all times choose between ethanol and water. Saline was injected ip once a week. A control group (Group 4) was not exposed to ethanol. During the following evaluation period, lasting 30 weeks, Groups 1, 2 and 3 had, except for a 3 week period, continuous access to ethanol. Different concentrations of ethanol were tested. Group 4 had access to 30% ethanol only for one week. At the end of the experiment, nicotinic and muscarinic binding sites (total, measured with QNB, M1 and M2) were determined in brain cortex, striatum and medulla + midbrain. During the treatment, voluntary ethanol intake in Group 1 was inhibited compared to Group 2 with a maximum around week 5 and a return to the level of Group 2 after 15-20 weeks. After a 3 week interruption of access to ethanol during the evaluation period, intake of ethanol was increased in Groups 1, 2 and 3. The increase was independent of prior intake in Groups 1 and 2 and proportional to prior ethanol intake in Group 3, where the largest increase was seen in rats with the largest intake prior to interruption. During testing of different concentrations (5 and 20%) no change in individual intake was seen. Thus a short abstinence from ethanol was a way to increase voluntary ethanol intake with a more specific effect than a mere change of concentration. No differences between groups were seen in muscarinic or nicotinic binding in brain. The muscarinic receptor binding in striatum and medulla + midbrain positively correlated with ethanol intake in Group 3. The nicotinic receptor binding in the cortex of Groups 1 and 2 positively correlated with water intake recorded during the last week of the evaluation period. The muscarinic M1 and M2 binding sites were positively correlated in the striatum in all groups, but differences between the groups were also seen in the correlation pattern within or between brain parts.