Acute administration of benzodiazepines in normal volunteers simulates the type of cognitive impairment (dysfunction in reflective (control) cognitive operations) found in detoxified alcoholics and potentiates the cognitive deficit found in those patients. Normal volunteers, treated with the benzodiazepine triazolam, are unable to effectively, strategically, shift their attention, are not able to appreciate the extent to which they are sedated, cannot monitor the accuracy or the source of what they remember, and are unable to suppress errors in performing cognitive tasks despite the fact that many other facets of their cognitive functioning are spared. The effect of acute alcohol administration on cognition are similar to those expressed by benzodiazepines and are different from the cognitive effects of other classes of drugs, i.e., cholinergic antagonists, but are similar to the effects of ketamine, an antagonist of the NMDA-type glu receptor, a receptor believed to be involved in long-term potentiation (memory consolidation). Drugs such as benzodiazepines, and alcohol in normal controls, also produce qualitative shifts in how they retrieve previously acquired knowledge. That is, these types of drugs alter retrieval context which is manifest in the specific facets of previously acquired experiences that can be recalled. This is expressed in various forms such as state (context)-dependent retrieval of self-generated information, memory for the source of knowledge, and evaluation of intrusion errors. Paradoxically, the presence of these drugs at the time of retrieval can enhance the amount of information that can be remembered for information acquired just prior to drug administration. The profile of highly specific effects of benzodiazepines (and alcohol) on reflective functions may be important in understanding patterns of uncontrolled drinking in alcoholics and also provides data on the stimulus discriminative (and reinforcing) properties of these drugs. This research is being extended to the study of alcohol craving and the study of children that are at risk for alcoholism.
