In our continuing effort to characterize the discriminative stimulus effects of ethanol, we studied the ability of various receptor agonists and antagonists to substitute for or antagonize the ethanol cue. Blockade of the discriminative stimulus effects of ethanol in pigeons by antagonists of the 5-HT3 receptor/ion channel complex was replicated in another species, rats. The discriminative stimulus effects of competitive and uncompetitive NMDA receptor complex antagonists were found to be similar to the discriminative stimulus effects of ethanol. Agonists at the GABAA receptor complex were also found to have similar discriminative stimulus effects as ethanol. The results imply that (2) 5-HT3 mediated neurotransmission is necessary for the mediation of the discriminative stimulus effects of ethanol and that (2) antagonism of the NMDA receptor or potentiation of the GABAA receptor complex result in discriminative stimulus effects similar to those of ethanol. In a separate set of studies we have investigated the influence of vasopressin in the process of information retention using a T-maze alternation task. Rats that are homozygous or heterozygous for a gene with a single base-pair substitution in the region encoding for the hormone vasopressin (the diabetes insipidus (di) gene) were compared to rats with a normal gene for vasopressin. There is a clear difference in the amount of delay the 3 groups of rats can tolerate before their ability to alternate their responses in the T-maze is impaired. The results show that vasopressin is not necessary for performance or ability to learn the task, but is crucial for the animals to retain information. Since tolerance can be viewed as an adaptation to ethanol that is retained over time, these data support the hypothesis that vasopressin is necessary for the maintenance, but not the production, of tolerance to ethanol.
