In the present study, the possible effect of nitric oxide agents injected into the nucleus accumbens (NAc) in the presence or absence of nicotine on morphine state-dependent memory in adult male Wistar rats was investigated. As a model of memory, a step-through type inhibitory avoidance task was used. Post-training injection of morphine (4 and 6 mg/kg) dose dependently induced the impairment of memory retention. Administration of morphine (4 and 6 mg/kg) before retention induced state-dependent retrieval of the memory acquired under post-training morphine (6 mg/kg) influence. Injection of nicotine before retention (0.25 and 0.5 mg/kg) alone and nicotine (0.1, 0.25 and 0.5 mg/kg) plus an ineffective dose of morphine (2 mg/kg) reversed the post-training morphine-induced memory impairment. The amnesia elicited by morphine (6 mg/kg) was also prevented by pre-retention intra-NAc administration of a nitric oxide synthase (NOS) inhibitor, l-NAME (0.24 μg/rat, intra-NAc). Interestingly, an ineffective dose of nicotine (0.1 mg/kg) in combination with low doses of l-NAME (0.06 and 0.12 μg/rat, intra-NAc) synergistically improved memory performance impaired by morphine given after training. It is important to note that intra-NAc administration of l-NAME before retention impaired memory retrieval by itself. In contrast, pre-retention administration of l-arginine, a nitric oxide (NO) precursor (0.25 and 0.5 μg/rat, intra-NAc), which had no effect alone, prevented the nicotine reversal of morphine effect on memory. The results suggest a possible role for nitric oxide of nucleus accumbens in the improving effect of nicotine on the morphine-induced amnesia and morphine state-dependent memory.Highlights
▸ Pre-test injection of nicotine and/or morphine reverse morphine induced amnesia. ▸ Morphine amnesia was also prevented by pre-test intra-NAc injection of l-NAME. ▸ Ineffective dose of nicotine potentiate l-NAME effect on morphine amnesia. ▸ Injection of l-arginine prevented improving effect of nicotine on morphine amnesia.