INHIBITORS OF PLA(2) AND NO SYNTHASE COOPERATE IN PRODUCING AMNESIA OF A SPATIAL TASK

BOTH nitric oxide and arachidonic acid have been suggested to play a r ole as a retrograde messenger in synaptic plastic changes which underl ie memory formation. However. inhibitors of nitric oxide (NO) synthesi s or of arachidonic acid release have produced contradictory results. We suggest a model which involves simultaneous release of both messeng er types which can compensate for the loss of one type. To test this t heory, rats were injected either with a drug that inhibits release of arachidonic acid, or a drug that inhibits synthesis of NO, or with bot h drugs. Acquisition of a water maze task was not different between gr oups. In the test sessions, however, animals injected with both drugs showed marked amnesic symptoms, while the groups injected with a low d ose of nordihydroguaiaretic acid (NDGA) or with nitro-L-arginine (L-NA RG) showed a trend towards amnesia. The effect of both drugs appears t o be additive. The results support the proposed theory.