| Background: The concept of craving is widely held to be essential for understanding the pathogenesis of addiction, and the mechanisms underlying relapse or reinstatement of drinking. Converging evidence suggests that neurochemistry, psychophysiology and clinical characteristics craving may result from distinct pathways, each of which can be identified through individual differences with respect. Objectives: The primary objective of this study is to examine the role of 1) opioidergic and glutamatergic/GABAergic to neurochemistry, psychophysiology and clinical characteristics. neurotransmission and 2) psychophysiological cue reactivity in two distinct pathways to craving. As a secondary Objectives: The primary objective of this study is to examine the role of 1) opioidergic and glutamatergic/GABAergic objective, we will identify clinical indicators of the pathways that could be used as predictors and treatment-matching neurotransmission and 2) psychophysiological cue reactivity in two distinct pathways to craving. As a secondary variables. Objective, we will identify clinical indicators of the pathways that could be used as predictors and treatment-matching. Expected outcomes: Most importantly, it is predicted that prototypical 'reward cravers' will differentially show a variables. Reduction of cue-induced craving in response to the opioid antagonist naltrexone, whereas prototypical 'relief cravers'. Expected outcomes: Most importantly, it is predicted that prototypical 'reward cravers' will differentially show a will differentially show a reduction of cue-induced craving in response to the glutamate antagonist (and, possibly, reduction of cue-induced craving in response to the opioid antagonist naltrexone, whereas prototypical 'relief cravers' GABA agonist) acamprosate. Furthermore, it is expected that changes in response to the respective anti-craving will differentially show a reduction of cue-induced craving in response to the glutamate antagonist (and, possibly, compounds can be predicted through clinical indicators such as personality traits, and drinking history/patterns.GABA agonist) acamprosate. Furthermore, it is expected that changes in response to the respective anti-craving Global research design and subjects: The proposed project concerns a human experimental study among 60 compounds can be predicted through clinical indicators such as personality traits, and drinking history/patterns. residentially-treated male alcoholics, who will be selected from a consecutive series of 200 patients based on their Global research design and subjects: The proposed project concerns a human experimental study among 60 scores on a multidimensional craving questionnaire. Included will be 30 'prototypical' reward cravers and 30 residentially-treated male alcoholics, who will be selected from a consecutive series of 200 patients based on their 'prototypical' relief cravers. These subjects participate in a series of cue exposure experiments both preceding and scores on amultidimensional craving questionnaire. Included will be 30 'prototypical' reward cravers and 30 following randomized, placebo-controlled 10-day challenges with naltrexone and acamprosate. In addition to the 'prototypical' relief cravers. These subjects participate in a series of cue exposure experiments both preceding and experimental studies, all 200 subjects will be administered several questionnaires measuring craving, personality, following randomized, placebo-controlled 10-day challenges with naltrexone and acamprosate. In addition to the drinking history and patterns, etc.experimental studies, all 200 subjects will be administered several questionnaires measuring craving, personality, Scientific and clinical relevance: The current research has considerable relevance with respect to understanding the drinking history and patterns, etc. neurobiological mechanisms of craving, the reduction of craving through pharmacotherapy, and the potential of Scientific and clinical relevance: The current research has considerable relevance with respect to understanding the matching patients to treatments through the recognition of individual differences. Neurobiological mechanisms of craving, the reduction of craving through pharmacotherapy, and the potential of matching patients to treatments through the recognition of individual differences. |
