Temporal studies of the inhibition of voluntary ethanol intake in the rat induced by intermittent ethanol treatment and some long term neurochemical consequences.

Male rats were injected with ethanol (groups 3 and 5; 2.0 g/kg i.p.) or saline (groups 2 and 4) once a week for 52 weeks. The rats had access to ethanol as a voluntary choice for 24 h either once 6 days after the injection (groups 2 and 3) or twice 3 and 6 days after the injection (groups 4 and 5). At the beginning of the treatment ethanol injections inhibited voluntary ethanol intake if tested 6 days later (groups 3 and 5), but a tolerance developed to this inhibition. During tolerance development the rats in group 5 also drank less ethanol on day 3 than on day 6. No corresponding behaviour was seen in group 4. Thus part of the tolerance was a gradual reduction of the duration of inhibition. During the evaluation period (25 weeks) after the treatment, ethanol exposure (20 weeks) consisted of a continuous choice between ethanol and water. Of different ethanol concentrations both ethanol-injected groups (3 and 5) took the same voluntary dose of ethanol independent of the offered concentration. After 5 weeks without ethanol all rats were killed and a number of neurochemical variables were determined. Compared with almost unexposed rats (group 1) changes were seen in inositol phospholipid breakdown, muscarinic binding sites in hippocampus, noradrenaline concentrations in frontal cortex, hippocampus and hypothalamus, dopamine concentration in frontal cortex and 5-hydroxytryptamine concentration in hypothalamus. In most cases the largest changes were seen in group 5. None of the variables had a constant relation to ethanol intake in the total population. However, significant correlations were found in some of the groups.