Inhibition of dorsal hippocampal nitric oxide synthesis potentiates ethanol-induced state-dependent memory in mice.

摘要

In an effort to understand the involvement of dorsal hippocampal nitric oxide system in ethanol (ETOH)-induced state-dependent memory, the effects of microinjection of l-arginine (a precursor of nitric oxide) and/or l-NAME (a nitric oxide synthase inhibitor) into the CA1 regions of dorsal hippocampus on this kind of memory were examined. In order to assess memory retrieval, a single trial step-down inhibitory avoidance task was used in mice. Pre-training intraperitoneal administration of ETOH (0.5 and 1g/kg) dose dependently caused amnesia, while pre-test administration of the same doses of ETOH restored the retrieval and induced state-dependent memory. Pre-test microinjection of l-arginine (0.5, 0.75 and 1 microg/mouse), into the CA1 region of dorsal hippocampus (intra-CA1) had no effect on memory retrieval. However, pre-test intra-CA1 microinjection of the same doses of l-arginine interestingly inhibited ETOH-induced state-dependent memory. The maximum response was obtained with 1 microg/mouse of l-arginine. Furthermore, memory impairment was produced following pre-test intra-CA1 microinjection of l-NAME (0.5, 0.75 and 1 microg/mouse). Pre-test co-administration of a higher dose of l-NAME (1 microg/mouse, intra-CA1) with an ineffective dose of ETOH (0.25 g/kg), improved the memory retrieval. Pre-test intra-CA1 microinjection of l-arginine or l-NAME could not affect ETOH-induced amnesia. In addition, l-arginine-induced inhibition of the pre-test ETOH response was decreased by pre-test microinjection of l-NAME. The ensemble of these observations suggests that ETOH-induced state-dependent memory can be modulated through the dorsal hippocampal nitric oxide system.