Effects of repeated withdrawal from chronic ethanol on oral self-administration of ethanol on a progressive ratio...

Male hooded Lister rats were trained using a sucrose-fading technique, to perform an operant lever press response to obtain ethanol. Initial training, using an FR4 schedule in which each reinforcement required four lever presses, included varying the concentration of ethanol in the liquid reinforcer. Changes in reinforcer concentration between 7 and 15% (vol/vol) had little effect on either numbers of lever pressing responses, or reinforcers obtained during the 3h session. Increasing the reinforcer concentration to 20% caused a decline in responding. The effects of varying reinforcer concentration (0-20% ethanol) were also studied in the same animals performing a progressive ratio schedule, in which the number of responses required to obtain a reinforcer was successively increased during the session. In these experiments the point at which rats ceased to respond (breaking point) was taken as a measure of their motivation to obtain ethanol. The function describing the relationship between ethanol concentration and number of responses, and number of reinforcers obtained in a session was an inverted U, with the maximum values occurring at an ethanol concentration of 10%. The value of the breaking point (highest ratio achieved) depended on the criterion used to define cessation of responding, but was between 15 and 22. Rats performing for ethanol showed higher breaking points than when responding for water, but there was no statistically reliable effect of ethanol concentration on the breaking point parameter. The effects of feeding the rats a liquid diet containing ethanol, and its subsequent withdrawal, on progressive ratio responding for 5% ethanol, were studied over four cycles of exposure and withdrawal. Intakes of ethanol of 11 g/kg/day had no effect on the animals' breaking point on the progressive ratio schedule, but withdrawal from the ethanol diet resulted in breaking points significantly higher than those in a control group pair-fed a nutritionally equivalent, ethanol-free diet. Although there was no further effect of repeated exposure and withdrawal on responding during the acute withdrawal phase, baseline levels of responding were elevated in the animals which had received multiple cycles of ethanol diet and withdrawal. These results are discussed in the context of the consequences of sensitization to repeated withdrawal from ethanol in dependent animals and humans.