Alcohol Clin Exp Res. 2004 Nov;28(11):1676-82.
O’Dell LE1, Roberts AJ, Smith RT, Koob GF.
Ethanol self-administering rats exhibit enhanced responding during withdrawal from continuous exposure to ethanol vapor. This study compared self-administration of ethanol during withdrawal from continuous versus intermittent ethanol vapor.
Experiment 1 examined self-administration of ethanol in rats trained to self-administer ethanol after continuous, intermittent (14 hr on and 10 hr off), or no (i.e., controls) ethanol vapor exposure. Exposure time was equalized such that the intermittent group received 4 weeks of exposure and the continuous group received 2 weeks of exposure. Four self-administration tests were conducted 2 hr after removal from vapor, and each test was separated by 3 to 4 days of ethanol vapor. Experiment 2 examined self-administration of ethanol after 2 weeks of intermittent vapor either 2 or 8 hr after removal from vapor. Experiment 3 addressed the specificity of the increased responding for ethanol by examining saccharin self-administration after 2 weeks of intermittent vapor.
Four weeks of intermittent exposure produced an increase in ethanol self-administration during the first withdrawal relative to controls and relative to animals receiving 2 weeks of continuous exposure. The continuous group was indistinguishable from controls on the first test and gradually increased their responding across tests. Two weeks of intermittent exposure also increased ethanol self-administration, and there was no difference in this effect 2 or 8 hr after removal from vapor. There was no difference in saccharin self-administration in control rats and those given 2 weeks of intermittent exposure.
The finding that intermittent exposure produces more rapid increases in self-administration of ethanol relative to continuous exposure suggests that intermittent exposure may be associated with a more rapid escalation of the allostatic processes responsible for excessive ethanol self-administration. The mechanisms that drive the increases in drinking during withdrawal are similar after 2 and 8 hr of withdrawal and seem to be specific to ethanol.