Subjective Response and Acute tolerance to Alcohol

Another important risk factor for alcohol-related problems that is best captured using lab-based alcohol administration paradigms is subjective response to alcohol. Previous alcohol challenge studies have shown that a low subjective response to alcohol is associated with both a family history of alcoholism and increased risk for the development of AUDs (Schuckit, 1994; Schuckit & Smith, 2000).  Although studies have consistently demonstrated the importance of a low level of response, previous research has focused primarily on effects that occur on the descending limb of the blood alcohol curve. This “snapshot” approach may miss important aspects of subjective response and potentially lead to erroneous conclusions.   Results of a recent study I conducted in collaboration with colleagues at The University of Texas demonstrate the importance of assessing subjective response at multiple time points (Corbin, Fromme, & Bergeson, 2006). In contrast to a previous study which assessed the relation between the serotonin transporter (SERT) gene and subjective response at only one time point, we assessed subjective response while blood alcohol levels were rising, and again when they were falling. No relation between the SERT and subjective response was found at either time point, but individuals with one or more long allele of the SERT (LS or LL) demonstrated more rapid development of acute tolerance (greater change in response from the first to the second assessment). The results suggest that the low subjective response identified as a risk factor in prior studies may actually reflect differences in acquired tolerance. Differences in acquired tolerance by family history may reflect greater alcohol-related neurotoxicity which may contribute to the development of dependence (Heinz et al., 2001). To further test this hypothesis, it is critical that studies of subjective response use multiple assessments across the blood alcohol curve. Such studies are also important because comparatively little attention has been given to more rewarding alcohol effects like stimulation that occur as blood alcohol levels rise.

In contrast to research demonstrating that a low-level of response to alcohol confers risk, the available research on stimulant alcohol effects suggests that those at high risk (e.g. those with a family history of alcoholism) actually experience greater stimulation. Such results led Newlin and Thomson (1990) to develop the “Differentiator Model” which suggests that the highest risk should be present for individuals with an enhanced stimulant response and a reduced sedative response. Presumably, alcohol is more reinforcing for these individuals because they receive more rewarding alcohol effects and fewer aversive alcohol effects. Important tenants of this model are that stimulant effects are rewarding to most individuals and that greater stimulant response should predict increased alcohol use. Consistent with the Differentiator Model, results of a recent study in my lab indicated that stimulant effects were evaluated much more positively than sedative effects, and that greater stimulant (but not sedative) response predicted increased within session drinking behavior (Corbin, Gearhardt, & Fromme, 2007). The results of this and other studies have begun to build a case for the importance of stimulant responses. Yet, many aspects of the Differentiator Model remain untested due to a paucity of studies assessing subjective response across the full blood alcohol curve and inadequate measures. To address the latter issue, one of my graduate students, Meghan Morean, is working with me to develop a new measure of subjective response that captures the full valence by arousal matrix of alcohol effects on both the ascending and descending limbs of the blood alcohol curve.