Enhanced Alcohol Self‐Administration after Intermittent Versus Continuous Alcohol Vapor Exposure

Abstract

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.

Dependence‐Induced Alcohol Drinking by Alcohol‐Preferring (P) Rats and Outbred Wistar Rats

“…This procedure has been described in detail elsewhere (O'Dell et al, 2004). Briefly, 95% ethanol was evaporated and vapor was delivered at rates between 22 and 27 mg/l.…”

“…Briefly, 95% ethanol was evaporated and vapor was delivered at rates between 22 and 27 mg/l. Ethanol vapor was turned on (6 PM) for 14 hour per day and off (8 AM) for 10 hour per day (O'Dell et al, 2004) for 4 consecutive weeks, and the target range for BALs during vapor exposure was 150 to 200 mg%. Nondependent control rats were treated in parallel except they were exposed to control air.…”

“…Tail blood samples were collected periodically at 8 AM for BAL determination and vapor adjustments during vapor exposure. This chronic intermittent vapor exposure produces somatic and motivational aspects of alcohol dependence during alcohol withdrawal (O'Dell et al, 2004).…”

“…The motivational factors that drive relapse alcohol drinking in humans last well into protracted abstinence (Hershon, 1977;VoltaireCarlsson et al, 1996). Many alcohol vapor studies have examined dependence-induced drinking in animals allowed to self-administer alcohol during acute withdrawal (2 to 12 hours), usually following approximately 4 weeks of alcohol vapor inhalation (Funk et al, 2006(Funk et al, , 2007O'Dell et al, 2004;Richardson et al, 2008;Roberts et al, 1996;Walker and Koob, 2007). Recently, it was shown that longer periods (≥8 weeks) of chronic intermittent alcohol vapor exposure produce dependence-induced increases in alcohol drinking that persist well into the abstinence period (Sommer et al, 2008), in agreement with an earlier study that showed protracted elevations in alcohol responding following a shorter period of vapor exposure (∼3 weeks; Roberts et al, 2000).…”

Increased Drinking During Withdrawal From Intermittent Ethanol Exposure Is Blocked by the CRF Receptor Antagonist d‐Phe‐CRF(12–41)

“…Subsequent studies determined that this increase in ethanol intake was more pronounced when the ethanol exposure (typically to ethanol vapor) to induce physical dependence was intermittent (O'Dell et al, 2004). Recent work in C57BL/6 (B6) mice also documented that intermittent ethanol vapor exposure significantly increased subsequent ethanol self-administration, measured during a limited access 2-bottle test (Becker and Lopez, 2004;Lopez and Becker, 2005) and operant (A. J.…”