Intraventricular 5,7-dihydroxytryptamine lesions disrupt acquisition of working memory task rules but not performance once learned

The serotonergic system is implicated in learning and memory and its disorder, e.g. after 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) abuse. This study examined the effects of widespread depletion of serotonin (5-HT) using intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) on the learning of a working memory task in the dark agouti (DA) rat. The lesion impaired acquisition but not later performance of a nonspatial working memory rule, as measured using nonmatch to sample object recognition in the Y-maze. The lesion had a marginal effect on choice completion times over the course of testing. However, nonspecific effects did not provide a good account of the reduction in choice accuracy as this persisted when completion times were taken into account statistically. Similarly, in a second experiment, the same lesioned rats were slowed in the acquisition of spatial alternation in the T-maze. However, in the open field, there were no comparably long-lasting effects of the serotonergic depletion on line crossings and defecation, only a transient reduction in activity on the first day. Together, these data suggest that the serotonergic system is important in the acquisition of working memory tasks in the rat and that this outcome was unlikely to be the result of nonspecific effects of the lesion.