Effects of Nω-Nitro-L-Arginine Methyl Ester on the Process of Memory Formation in the Discrimination Learning in Rats

【目的】一酸化窒素(NO)は学習・記憶に何らかの関与をしていることが考えられているものの,詳細な分子機序は充分に解明されていない.そこで,学習・記憶の形成過程におけるNOの果たす役割について明らかにする目的で行動科学実験を行った.【方法】ラットの明暗弁別学習課題を用いて,NO合成酵素阻害薬であるNω-nitro-L-arginine methyl ester(L-NAME)投与の影響を検討した.【結果】L-NAME(30 mg/kg, i.p.)を学習課題終了直後に投与すると,非活性型光学異性体D-NAMEに比べ,有意に学習成績を低下させた.また,記憶に関連の深い海馬におけるNO濃度が有意に低下していた.【考察】ラットの明暗弁別学習獲得過程に少なくとも海馬におけるNOが関与していることが示唆された.【結論】NOはラットの弁別学習の獲得ならびに記憶の固定に重要な役割を果たしているものと考えられた.
Nitric oxide (NO) is considered to be a possible retrograde messenger involved in synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD). The role of NO in LTP and / or LTD has suggested that NO may also play a role in the process of learning and memory. We examined the effects of Nω-nitro-L-arginine methyl ester (L-NAME) on discrimination learning behavior. L-NAME is one of the major drugs with a non-selective inhibitory effect on NO synthase (NOS). In the present study, treatment with L-NAME (30 mg/kg, i.p.), but not D-NAME (30 mg/kg, i.p.), an inert isomer of L-NAME, significantly reduced the averaged discrimination ratios for the last 6-session block. In contrast, the overall response rate was markedly increased by both L-NAME and D-NAME treatment, but the effect was not significant. These findings suggest that L-NAME influences the process of memory formation in discrimination learning and that NO may play an important role in discrimination learning behavior, particularly at the acquisition and consolidation stage of memory formation.