Analysis of the avoidance learning deficit induced by the serotonin releasing compound p-chloroamphetamine

The effects of the serotonin-releasing compound p-chloroamphetamine (PCA, 2.5 mg/kg) on avoidance acquisition, retention and memory retrieval were examined in male Sprague-Dawley rats using a one-way active avoidance and a one-trial passive avoidance task. The drug was injected IP prior to training, following acquisition and prior to the retention test 24 hr after training using a state-dependent design. In the normal context situation pretraining administration of PCA markedly impaired active avoidance acquisition, but PCA-treated rats did not differ from controls in their retention performance when tested 24 hr after training. In the dark/light box test pretraining administration of PCA caused a dose-dependent impairment of both active and passive avoidance retention which could not be explained in terms of changes in locomotor activity or behavioural disinhibition at the time of testing or state-dependent retention. Post-training administration of PCA failed to affect avoidance retention in both tasks. The drug was found to impair memory retrieval in a dose- and time-dependent fashion in the one-way active but not in the passive avoidance test. Pretraining administration of PCA produced a progressive loss of passive and active avoidance performance at increasingly longer retention intervals. The present results suggest that serotonin has dual effects on processes underlying learning and memory involving effects on both associative and non-associative learning processes in the rat. The time-dependent loss of memory retention following 5-HT release indicates that serotonin has a role in the way information is processed in the brain.