Chapter 4 - Imbalance between neuroexcitatory and neuroinhibitory amino acids causes craving for ethanol: From animal to human being studies

Abstract

This chapter describes the role of imbalance between neuroexcitatory and neuroinhibitory amino acids in causing craving for ethanol. The hypofunction of GABAA receptors and enhanced function of NMDA receptors are suggested to be responsible for ethanol withdrawal symptoms. Multiple and repeated periods of chronic ethanol consumption and withdrawal often occur in alcohol abusers. It is suggested that animal studies on the changes in glutamate following chronic ethanol treatment (CET) that is interrupted by repeated ethanol withdrawal episodes may be of clinical relevance for the development of treatment strategies. The elevated glutamate released in the hippocampus during the first cycle of ethanol withdrawal episode was exacerbated in subsequent withdrawal episodes. Acamprosate, a drug used during human alcohol detoxification, is able to completely block the glutamate increase observed during the first as well as the third withdrawal of ethanol. It is found that when repeated ethanol injections were cued with a vinegar stimulus that had previously been associated with the same ethanol injection, a significant increase in glutamate microdialysate content was assayed. It is suggested that the conditioned responses by extracellular glutamate concentrations may participate in the environmental cue-induced conditioned cravings for ethanol that are thought to be related to the high frequency of relapse in detoxified alcoholics.