EFFECTS OF SELECTIVE CATECHOL-O-METHYLTRANSFERASE INHIBITORS ON SINGLE-TRIAL PASSIVE-AVOIDANCE RETENTION IN MALE-RATS

The effects of new selective catechol-O-methyltransferase (COMT) inhib itors entacapone (mainly peripheral effect) and tolcapone (acting also in the brain) on normal and impaired cognitive functions were studied in aversively motivated inhibitory avoidance using a single-trial pas sive avoidance paradigm in young adult rats. Passive avoidance retenti on latency was shortened by either scopolamine (1.0 mg/kg) or bilatera l lesions to nucleus basalis magnocellularis (NBM) caused by infusions of ethylcholine aziridinium (AF64A). Entacapone (30 mg/kg) administer ed once before training or before the retention test, 24 h after train ing, prevented the effect of scopolamine but did not alter extinction in these rats. However, entacapone (30 mg/kg) prolonged lag time when given during the extinction process to intact rats after training. Tol capone administered once before training (10 mg/kg) counteracted the e ffect of scopolamine. It prolonged retention latency of the intact rat s when given after training (10 mg/kg). Tolcapone (3 mg/kg) also prolo nged lag time when given during extinction to rats bearing NBM lesions . The effect of scopolamine on extinction and retrieval was not preven ted by tolcapone. Only entacapone improved memory storage. Collectivel y, the present results indicate that COMT inhibitors prolong retention latencies in a single-trial passive avoidance test assessed at severa l memory phases. (C) 1997 Elsevier Science B.V.