Inhibitors of PLA2 and NO synthase cooperate in producing amnesia of a spatial task.
Both nitric oxide and arachidonic acid have been suggested to play a role as a retrograde messenger in synaptic plastic changes which underlie memory formation. However, inhibitors of nitric oxide (NO) synthesis or of arachidonic acid release have produced contradictory results. We suggest a model which involves simultaneous release of both messenger types which can compensate for the loss of one type. To test this theory, rats were injected either with a drug that inhibits release of arachidonic acid, or a drug that inhibits synthesis of NO, or with both drugs. Acquisition of a water maze task was not different between groups. In the test sessions, however, animals injected with both drugs showed marked amnesic symptoms, while the groups injected with a low dose of nordihydroguaiaretic acid (NDGA) or with nitro-L-arginine (L-NARG) showed a trend towards amnesia. The effect of both drugs appears to be additive. The results support the proposed theory.
Hölscher
C
C
Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland.
Canevari
L
L
Richter-Levin
G
G
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000648:Amnesia, Retrograde / Q000139:chemically induced*; D000818:Animals; D004347:Drug Interactions; D009637:Masoprocol / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects*; D019001:Nitric Oxide Synthase; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar
D009637:Masoprocol; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010741:Phospholipases A; D054467:Phospholipases A2