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) inhibitors 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 passive avoidance paradigm in young adult rats. Passive avoidance retention latency was shortened by either scopolamine (1.0 mg/kg) or bilateral lesions to nucleus basalis magnocellularis (NBM) caused by infusions of ethylcholine aziridinium (AF64A). Entacapone (30 mg/kg) administered once before training or before the retention test, 24 h after training, 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. Tolcapone administered once before training (10 mg/kg) counteracted the effect of scopolamine. It prolonged retention latency of the intact rats when given after training (10 mg/kg). Tolcapone (3 mg/kg) also prolonged lag time when given during extinction to rats bearing NBM lesions. The effect of scopolamine on extinction and retrieval was not prevented by tolcapone. Only entacapone improved memory storage. Collectively, the present results indicate that COMT inhibitors prolong retention latencies in a single-trial passive avoidance test assessed at several memory phases.
Khromova
I
I
Russian Academy of Medical Sciences, Institute of Pharmacology, Moscow, Russia.
Voronina
T
T
Kraineva
V A
VA
Zolotov
N
N
Männistö
P T
PT
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D001388:Aziridines / Q000494:pharmacology; D001577:Benzophenones / Q000494:pharmacology; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000502:physiology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009570:Nitriles; D009596:Nitrophenols; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012153:Retention, Psychology / Q000187:drug effects* / Q000502:physiology; D012601:Scopolamine / Q000494:pharmacology; D013377:Substantia Innominata / Q000187:drug effects / Q000502:physiology; D000077867:Tolcapone
D000978:Antiparkinson Agents; D001388:Aziridines; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D009466:Neuromuscular Blocking Agents; D009570:Nitriles; D009596:Nitrophenols; C071192:entacapone; C044894:ethylcholine aziridinium; D000077867:Tolcapone; D012601:Scopolamine; D002394:Catechol O-Methyltransferase; D002794:Choline