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Odor cues used to explore stress-alcohol connection by Ann Lacy Special to The Catalyst While the scent from a fresh slice of lime makes some people reach for a cool gin and tonic, the odor of lemon may induce certain members of the MUSC rodent population to crave a drink as well. Marcelo Lopez, Ph.D., is experimenting with the lemon scent as a cue prior to stress in mice which have a genetic propensity for alcohol. Lopez is the lead investigator in a pilot project to determine in an animal model how exposure to certain stimuli associated with stress can have an impact on alcohol relapse.  Historically, the connection between stress and alcohol abuse in humans, while seemingly self-evident, has not been validated scientifically. Studies in humans, like the work of MUSC’s Alcohol Research Center researcher Kathleen Brady, M.D., Ph.D., on alcoholics with post-traumatic stress disorder, may benefit greatly from research at the basic science level on animal models. The novelty of  Lopez’s approach is his focus on the stimuli or cues rather than the stress itself.  Since the trauma of the stress may have some physiological effects leading to alcohol consumption, he is seeking to eliminate any trauma and establish whether a non-invasive cue alone can produce physiological change.  Lopez is a post-doctoral fellow doing research in MUSC’s Alcohol Research Center, one of only 15 nationally funded alcohol research centers in the United States. The project, which runs from July 2001 to July 2003, is funded by the National Institute on Alcohol Abuse and Alcoholism, a division of the National Institutes of Health.  Lopez is working under the direction of the ARC’s director, Carrie Randall, Ph.D., co-scientific director Howard Becker, Ph.D., and Ron See, Ph.D., of the Department of Physiology and Neuroscience.  In his experimental protocol, the cues Lopez has chosen are odor cues, specifically fruit scents like lemon and banana. Such scents were chosen because they were unfamiliar to laboratory mice and not inherently repellent to them. The optimal stressors have yet to be determined. However, all the experimental environmental stressors currently being tested were not previously known to the mice. In one set of experiments, the mice (strain C57BL/6J, genetically predisposed to like alcohol) are all provided with alcohol to drink for two hours daily until a stable level of intake is established. Then for one week the mice go on the wagon. They are deprived of alcohol and divided into three groups. The control group is exposed to neither odor nor stress. The other two groups are exposed for 15-minute intervals to the same odor cue  (lemon). After exposure, one of these latter groups is stressed immediately and the second group six or seven hours later. Following this week-long training procedure, the mice are again allowed to imbibe for two hours daily. After several days of alcohol consumption, all three groups (the controls, the cue-immediate stress group, and the cue-delayed stress group) are exposed to the lemon scent.  Studies are then performed to determine whether simply presenting the odor activates a physiological response to stress, even in the absence of the actual stress event. Lopez explained that “we expect that for the cue-immediate stress group, the cue presentation will increase their stress level (measured by corticosterone levels on plasma) and increase alcohol intake.” Once it has been established that exposure to the cues minus the stress does induce a neurobiological response which increases the mice’s physiological vulnerability to alcohol, Lopez will attempt to determine strategies which can lower the likelihood of the cues to increase the alcoholic mice’s desire for a drink.  He will develop a model to test therapeutic compounds like naltrexone to ultimately prevent stress-induced relapse. The NIH-mandated mission of MUSC’s Alcohol Research Center is treatment of people suffering from alcoholism.  Lopez’s work is a pilot project in which the National Institute of Alcohol Abuse and Alcoholism has invested seed money for the development of novel ideas that will ultimately aid in the treatment of the intractable problem of alcoholism in our society.