Introduction: Zinc oxide nanoparticles due to have special properties, in many products such as cosmetics, food additives and etc, are being used. These compounds reach the brain through the blood-brain barrier or the olfactory nerve pathway and damage the brain through oxidative stress, inflammatory responses and cytotoxicity. It has been shown that zinc oxide nanoparticles can induce changes in learning ability and memory by altering synaptic plasticity Nicotine receptors are present in various parts of the brain, including the hippocampus, and control synaptic plasticity through the release of various neurotransmitters, including acetylcholine, dopamine, and glutamate. Nicotinic receptors signaling pathways in the dorsal hippocampus may alsoinvolve in drug interactions and memory formation. In the present study, the effect of nicotinic receptors blockade in the dorsal hippocampus by mecamylamine on the effects of zinc oxide nanoparticles on passive avoidance memory and locomotor activity was investigated. Materials and methods: In this experimental study, adult male Wistar rats weighing 220-250 g were divided into control groups (saline 1 ml/kg), zinc oxide nanoparticles (0.5 mg/kg), mecamilamine (0.5 and 1 µg/rat) and mecamilamine (0.5 and 1 µg/rat) along with zinc oxide nanoparticles (0.5 mg/kg). In all groups, bilaterary cannulated was performed in CA1 region. Intracerebral injection of saline or mecamilamine immediately after training and intraperitoneal injection of saline or zinc oxide nanoparticles with 5 minutes interval was performed. Passive avoidance test was used to assess memory 24 and 72 hours after training. Motor activity was assessed at each stage after the behavioral test. Results: post-training injection of zinc oxide nanoparticles (0.5 mg/kg) had no significant effect on passive avoidance memory compared with control group (p> 0.05). Intrahippocampal injection of mecamylamine combined with ineffective dose of zinc oxide nanoparticles (0.5 mg /
