The effects of ACE inhibitors captopril and SQ29,852 in rodent tests of cognition.
The ACE inhibitors captopril and SQ29,852 enhanced a habituation response to bright illumination in young adult and aged mice measured in a two-compartment light/dark test box. The treatments also antagonised a scopolamine-induced impairment and SQ29,852 was approximately 100 times more potent than captopril. In rats trained on a reinforced alternation paradigm in a T-maze, aged rats, as compared to young adults, showed a reduction in choice performance which was antagonised by SQ29,852. The impairment in choice performance in the T-maze induced by scopolamine in young adult rats was antagonised by SQ29,852 whilst captopril only delayed the onset of the scopolamine-induced impairment. SQ29,852 also antagonised scopolamine-impaired escape latency in a spatial learning/memory paradigm in a water-maze test. The effects of SQ29,852 in the rat were achieved within a somewhat restricted dose range. The ability of captopril and SQ29,852 to increase performance in the behavioural tests is discussed in terms of an antagonism of angiotensin converting enzyme to remove an inhibitory role of angiotensin II on central cholinergic function.
Costall
B
B
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, UK.
Coughlan
J
J
Horovitz
Z P
ZP
Kelly
M E
ME
Naylor
R J
RJ
Tomkins
D M
DM
D000367:Age Factors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004347:Drug Interactions; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011392:Proline / Q000494:pharmacology / Q000031:analogs & derivatives; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D009943:Organophosphorus Compounds; D011392:Proline; D002216:Captopril; D012601:Scopolamine; C054518:ceronapril