RECOVERY AFTER INTERRUPTED EXPOSURE DURING INDUCTION OF EXPERIMENTAL ALCOHOLISM IN THE RAT

摘要

A model of alcoholism founded on a long-term treatment with intermittent weekly ethanol exposures [each week a voluntary choice between 10%(w/v) ethanol and water for 24 hr followed by an intraperitoneal (i.p.) injection of 2.0 g/kg ethanol] was used to test the effect of a 10-week interruption of the treatment. Three groups were tested. Group CT had 65 weeks of treatment with no interruption. Group BT started the treatment at the same time as group CT, but no treatment was given in weeks 33–42. In group LS, the treatment started at the same time as it was restarted in group BT (week 43). An evaluation period with a continuous choice between ethanol and water was started in week 66. During the evaluation period dependence, defined as a voluntary ethanol intake not influenced by changes in ethanol concentration, was determined by comparing the intake of a 10%(w/v) reference solution with that of a 5%(w/v) test solution. At the start of the treatment the 24 hr voluntary ethanol intake in group CT and BT was inhibited maximally after 6–7 weeks of treatment. When group LS was started in week 43, a similar, but more marked, inhibition developed. In all groups, ethanol intake rose again after the inhibition. After restarting the treatment in group BT, the rats could be divided into two subgroups. Group BT;LI with a low intake of ethanol in week 32 had voluntary ethanol intake after restarting the treatment which was similar to corresponding data recorded in group LS when starting the treatment. In group BT;HI with a high intake of ethanol in week 32 there was no influence of the break in the treatment. The voluntary ethanol intake was similar to the corresponding intake in group CT and not to that seen in group LS. During the evaluation period, a marked dependence was recorded as a strong correlation between voluntary intake of ethanol as a 5 and a 10%solution in group CT (r=0.93; N=11,P<0.001). A similar dependence but with a lower daily ethanol intake was recorded in group LS (r=0.88,N=9,P<0.01) after a treatment lasting for 22 instead of 65 weeks. A dependence was recorded in group BT;HI (r=0.97;N=4,P<0.05) but not in group BT;LI (r=0.63,N=7, NS). Thus rats with a low intake before the break of the treatment behaved as naïve rats starting the treatment but did not show dependence, while rats with a high intake before the break behaved in the same way as rats continuously exposed to ethanol with regard to the development of depend