ADDITIVE DEFICITS IN THE CHOICE ACCURACY OF RATS IN THE DELAYED NONMATCHING TO POSITION TASK AFTER CHOLINOLYTICS AND SEROTONERGIC LESIONS ARE NON-MNEMONIC IN NATURE

The role of serotonin (5-HT) and its interaction with the muscarinic o r nicotinic receptor-mediated mechanisms in the modulation of working memory and motor activity was investigated by assessing the effects of 5-HT lesion and cholinergic receptor blockade on the performance of r ats in a working memory (delayed non-matching to position, DNMTP) task . A global serotonergic lesion was induced by the intracerebroventricu lar adminstration of 5,7-dihydroxytryptamine (5,7-DHT). Post-mortem ne urochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in frontal and parietooccipital cor tices and in hippocampi of 5,7-DHT lesioned rats. 5-HIAA levels were a lso reduced in striatum. 5,7-DHT lesion slightly impaired choice accur acy of rats in the DNMTP task and also transiently reduced motor activ ity in rats. Even the lower dose of scopolamine (0.075 mg/kg), a musca rinic receptor antagonist, impaired the choice accuracy already at the shortest delay (i.e. not indicative of a working memory impairment pe r se), and caused a marked disruption of motor activity (lengthened re sponse latencies, increased probability of omissions and decreased tri als completed). Furthermore, the quaternary analogue, N-methylscopolam ine (0.150 mg/kg), affected the motor activity of rats to the same ext ent as scopolamine. Mecamylamine (1.0; 3.0 mg/kg) also interfered with motor activity and it slightly decreased the choice accuracy, which w as not dependent on the delay. Although mecamylamine disrupted the per formance of rats in the DNMTP task, the disruption was not as severe a s that seen with scopolamine. Moreover, both scopolamine and mecamylam ine augmented the slight impairment on the choice accuracy of 5,7-DHT lesioned rats, but this was non-mnemonic in character. We conclude tha t there is no evidence for any major interaction between the serotoner gic system and muscarinic or nicotinic cholinergic mechanisms in worki ng memory per se, but muscarinic and nicotinic receptor antagonists ma y act additively with the 5,7-DHT lesion to disrupt the choice accurac y of rats.