Alcohol Sensitizes Cerebral Responses to the Odors of Alcoholic Drinks : An fMRI Study

THE MESOCORTICOLIMBIC DOPAMINE (DA) system plays a prominent role in addiction to alcohol and other drugs of abuse (Gonzales et al., 2004; Robinson and Berridge, 1993). While alcohol itself has been reported to increase dopaminergic transmission in the ventral tegmental area (VTA) and nucleus accumbens (NAc; e.g., Brodie et al., 1999; Di Chiara and Imperato, 1988), recent research suggests that alcohol’s conditioned cues (e.g. the sight or smell of an alcoholic beverage) may be more responsible for eliciting DA activity in the NAc (Doyon et al., 2003, 2005; Katner et al., 1996; Katner and Weiss, 1999; Melendez et al., 2002). In addition, primate and human literature point to orbitofrontal cortex’s role in responding to rewards and their conditioned cues, and in a manner that varies according to reward satiety (Critchley and Rolls, 1996; O’Doherty et al., 2000; Gottfried et al., 2003). Alcohol-related olfactory cues may be powerful appetitive cues, particularly insofar as they are present both before (nasally) and during drinking (retronasally). This would make them effective conditioned cues of alcohol’s immediate reward. In support of that postulate, Grusser et al. (2000) found that the odor of brandy (although not beer), elicited a significant craving response. Rohsenow et al. (1994, 1997) showed that combined visual and olfactory cues elicited an urge to drink in 30 male alcoholics in treatment. Weinstein et al. (1998) similarly found that combined visual and olfactory cues provoked craving and elevated systolic blood pressure in 14 abstinent male alcoholics. Using fMRI, we showed that alcohol-related olfactory stimuli elicited greater activation particularly in the NAc than non-alcohol-related odors in heavy drinkers (Kareken et al., 2004). Priming with alcohol increases the desire to drink (De Wit and Chutuape, 1993; De Wit, 1996) and may have disinhibiting effects that lead to loss of control of drinking (Collins, 1993; Poulos et al., 1998; Bensley, 1991). This suggests the possibility that alcohol enhances sensory processing of alcohol-related cues in areas related to appetitive drive, such as the NAc and orbitofrontal cortex. While a number of authors have studied cerebral activity as a function of alcohol-associated cues (e.g., George et al., 2001; Kareken et al., 2004; Myrick et al., 2004; Tapert et al., 2004), none have done so in ways that permit studying how the pharmacologic effects of alcohol affect sensory cue processing. We used fMRI to study regional cerebral responses to the odors of alcoholic beverages during constant, low-level brain exposure to alcohol as pharmacokinetically modeled by the “Indiana Clamp” (Ramchandani et al., 1999b; O’Connor et al., 2000; Ramchandani et al., 1999a)—a technique that permits targeting and maintaining a specific arterial blood-alcohol concentration during imaging. Ten hazardous, nondependent drinkers were exposed to the odors of their preferred alcohol drinks (alcohol odors, AO), non-appetitive odorants (NApO; grass, leather), and appetitive control odors (ApCO; chocolate, grape) under both alcohol (clamped at 50 mg%) and placebo infusions. In light of our previous findings in which the NAc responded more to AO than NApO (Kareken et al., 2004), and in the context of literature describing orbital cortex’s role in reward, we hypothesized that priming exposure to alcohol would enhance the contrast between responses to alcoholic drink odors and responses to control odors in the NAc and orbitofrontal cortex.