Nicotine improves ethanol-induced impairment of memory: possible involvement of nitric oxide in the dorsal hippocampus of mice.
In the present study, the possible involvement of nitric oxide (NO) systems in the dorsal hippocampus in nicotine's effect on ethanol-induced amnesia and ethanol state-dependent memory was investigated. Adult male mice were cannulated in the CA1 regions of the dorsal hippocampus and trained on a passive avoidance learning task for memory assessment. We found that pre-training intraperitoneal (i.p.) administration of ethanol (1 g/kg) decreased inhibitory avoidance memory when tested 24 h later. The response induced by pre-training ethanol was significantly reversed by pre-test administration of the drug. Similar to ethanol, pre-test administration of nicotine (0.4 and 0.8 μg/mouse, intra-CA1) alone and nicotine (0.2, 0.4 and 0.8 μg/mouse) plus an ineffective dose of ethanol also significantly reversed the amnesia induced by ethanol. Ethanol amnesia was also prevented by pre-test administration of L-arginine (1.2 μg/mouse, intra-CA1), a NO precursor. Interestingly, an ineffective dose of nicotine (0.2 μg/mouse) in combination with a low dose of L-arginine (0.8 μg/mouse) synergistically improved memory performance impaired by ethanol given before training. In contrast, pre-test intra-CA1 microinjection of L-NAME (NG-nitro-L-arginine methyl ester), a nitric oxide synthase (NOS) inhibitor (0.4 and 0.8 μg/mouse), which reduced memory retrieval in inhibitory avoidance task by itself, in combination with an effective dose of nicotine (0.4 μg/mouse) prevented the improving effect of nicotine on memory impaired by pre-training ethanol. Moreover, intra-CA1 microinjection of L-NAME reversed the L-arginine-induced potentiation of the nicotine response. The results suggest the importance of NO system(s) in the CA1 regions of the dorsal hippocampus for improving the effect of nicotine on the ethanol-induced amnesia.
Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Lahijan Branch, Lahijan, Iran. raoufinasrin@yahoo.co.uk
N
N
Raoufi
M
M
Piri
A
A
Moshfegh
M-S
MS
Shahin
D000647:Amnesia / Q000139:chemically induced; D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*
D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D009569:Nitric Oxide; D000431:Ethanol; D009538:Nicotine