Metrifonate improves spatial navigation and avoidance behavior in scopolamine-treated, medial septum-lesioned and aged rats.

Abstract:

:We investigated the effects of acute p.o. pretraining treatment with an indirect acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation and passive avoidance behavior. Metrifonate (10-100 mg/kg, orally, p.o.) did not improve the water maze or passive avoidance performance of young intact rats. However, in young rats metrifonate over a broad dosage range (10-100 mg/kg, p.o.) was able to alleviate the adverse effects of scopolamine (a muscarinic acetylcholine receptor antagonist; 0.4 and 2.0 mg/kg in water maze and passive avoidance study, respectively) and medial septum-lesioning on spatial reference and working memory and passive avoidance performance. In old (23-month-old) rats, a defect of water maze and passive avoidance behavior was observed. In old rats, metrifonate improved spatial reference memory function in the water maze and also passive avoidance at 10-30 mg/kg, but the 3 mg/kg dose was ineffective. Very old (27-month-old) rats had a more severe impairment of water maze performance than old rats, and metrifonate 3-30 mg/kg did not improve their spatial navigation. These results show that metrifonate may over a wide range of doses stimulate cognitive functioning, but during advanced aging neurobiological defects develop that may mask some of the therapeutic effects of metrifonate in rats.

journal_name

Eur J Pharmacol

authors

Riekkinen P Jr,Schmidt B,Stefanski R,Kuitunen J,Riekkinen M

doi

10.1016/0014-2999(96)00336-6

subject

Has Abstract

pub_date

1996-08-08 00:00:00

pages

121-30

issue

2

eissn

0014-2999

issn

1879-0712

pii

0014-2999(96)00336-6

journal_volume

309

pub_type

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