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

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 1 g/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 mu g/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 ETON-induced state-dependent memory. The maximum response was obtained with 1 mu g/mouse of L-arginine. Furthermore, memory impairment was produced following pre-test intra-CA1 microinjection of L-NAME (0.5, 0.75 and 1 mu g/mouse). Pre-test co-administration of a higher dose of L-NAME (1 mu g/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. (C) 2010 Elsevier B.V. All rights reserved.