5-HT1a Receptor Involvement in Temporal Memory and the Response to Temporal Ambiguity.

It has previously been demonstrated that rats trained on the peak-interval procedure to associate two different cues with two different fixed interval schedules will generate a scalar peak function at an intermediate time when presented with the compound cue. This response pattern has been interpreted as resulting from the simultaneous retrieval of different temporal memories, and a consequential averaging process to resolve the ambiguity. In the present set of studies, we investigated the role that serotonin 1a receptors play in this process. In Experiment 1, rats were trained on a peak-interval procedure to associate the interoceptive states induced by saline and the 5-HT1a agonist, 8-OH-DPAT, with a 5 s or 20 s fixed-interval schedule signaled by the same tone cue (counter-balanced). While peak functions following administration of saline were centered at the appropriate time (5 s or 20 s), peak functions following administration of the agonist were centered around 7 s, irrespective of the reinforced time during training, suggesting agonist-induced disruption in selective temporal memory retrieval, resulting in increased ambiguity regarding the appropriate time at which to respond. In Experiment 2, rats were trained in a peak-interval procedure to associate a tone cue with a 10 s fixed interval and a light cue with a 20 s fixed interval. Administration of the 5-HT1a antagonist, WAY-100635, had no impact on timing when single cues were presented, but altered the intermediate, scalar, response to the stimulus compound, suggesting antagonist-induced disruption in the processes used to deal with temporal memory ambiguity. Together, these data suggest that manipulations of 5HT transmission at the 5-HT1a receptor cause changes in the temporal pattern of responding that are consistent with alterations in temporal memory processes and responses to temporal ambiguity.