Background: Drugs of abuse such as nicotine and morphine produce their effects through the stimulation of the mesolimbic dopaminergic pathway. Therefore, the present study aimed to evaluate the effect of pre-test injection of nicotine on morphine state-dependent learning as well as the effect of intra-nucleus accumbens (NAc) administration of D1 receptor antagonist on nicotine's effects in morphine state-dependent learning model.

Materials and Methods: This experimental study was performed on 200 male rats. Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride plus xylazine and then placed in a stereotaxic frame. Two stainless-steel cannuale were placed in the NAc shell. The behavioral testing was started using an inhibitory avoidance task and afterwards the step-through latency of entering into the dark compartment was measured as a criterion for the assessment of memory.

Results: Post-training injection of morphine induced amnesia. The post-training morphine-induced amnesia was restored by pre-test administration of the same doses of morphine and also nicotine. Moreover, the pre-test intra-NAc injection of SCH23390 prevented the nicotine reversal of morphine effect on memory.

Conclusion: The results of this study suggest that the dopamine D1 receptor of the NAc may play an important role in improving the effect of nicotine on morphine-induced amnesia.