Beneficial effect of prolyl oligopeptidase inhibition on spatial memory in young but not in old scopolamine-treated rats.
The effects of a novel prolyl oligopeptidase (POP) inhibitor KYP-2047 on spatial memory of young (3-month-old) and old (8- to 9-month-old) scopolamine-treated rats (0.4 mg/kg intraperitoneally) was investigated in the Morris water maze. In addition, the concentrations of promnesic neuropeptide substrates of POP, substance P and neurotensin in various brain areas after acute and chronic POP inhibition were measured in young rats. In addition, inositol-1,4,5-trisphosphate (IP(3)) levels were assayed in rat cortex and hippocampus after effective 2.5-day POP inhibition. KYP-2047 (1 or 5 mg/kg 30 min. before daily testing) dose-dependently improved the escape performance (i.e. latency to find the hidden platform and swimming path length) of the young but not the old rats in the water maze. POP inhibition had no consistent effect on substance P levels in cortex, hippocampus or hypothalamus, and only a modest increase in neurotensin concentration was observed in the hypothalamus after a single dose of KYP-2047. Moreover, IP(3) concentrations remained unaffected in cortex and hippocampus after POP inhibition. In conclusion, the behavioural data support the earlier findings of the promnesic action of POP inhibitors, but the mechanism of the memory-enhancing action remains unclear.
Jalkanen
Aaro J
AJ
Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland. aaro.jalkanen@uku.fi
Puttonen
Katja A
KA
Venäläinen
Jarkko I
JI
Sinervä
Veijo
V
Mannila
Anne
A
Ruotsalainen
Sirja
S
Jarho
Elina M
EM
Wallén
Erik A A
EA
Männistö
Pekka T
PT
D000375:Aging / Q000502:physiology; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018727:Muscarinic Antagonists; D009496:Neurotensin / Q000378:metabolism; D000085822:Prolyl Oligopeptidases; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013373:Substance P / Q000378:metabolism
D018727:Muscarinic Antagonists; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D013373:Substance P; D009496:Neurotensin; D015544:Inositol 1,4,5-Trisphosphate; C094211:JTP 4819; D012601:Scopolamine; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases