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Updated: Jan 25, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
μ-Opioid receptor in the CA1 involves in tramadol and morphine cross state-dependent memory
Saba Niknamfar1, Setareh Nouri Zadeh-Tehrani1, Mitra-Sadat Sadat-Shirazi1
1Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
In the present study, the effect of tramadol - an opioid painkiller drug with abuse potential- on amnesia and state-dependent memory and its interaction with the opioidergic system was investigated in male Wistar rats. Intra CA-1 administration of tramadol (0.5, 1, and 2 μg/rat) before training, dose-dependently decreased the learning ability in passive avoidance task. Amnesia induced by pre-train tramadol administration was significantly reversed by pre-test administration of tramadol (1 μg/rat). Pre-test administration of naltrexone (a μ-opioid receptor (MOR) antagonist) inhibited the effect of tramadol on memory retrieval. In addition, the pre-test administration of morphine (1 μg/rat, intra-CA1) also reversed memory impairment induced by pre-train tramadol administration. Although, pre-train morphine administration (1 μg/rat, intra-CA1), induced memory impairment reversed by pre-test tramadol administration (1 μg/rat, intra-CA1). In addition, the level of MOR in the hippocampus decreased in animals with memory impairment due to using tramadol in the training day. However, state-dependent retrieval using tramadol or cross state-dependent retrieval using morphine enhanced the MOR level in the hippocampus. The results of the study suggested that intra-CA1 tramadol administration induced memory impairment, improved by pre-test administration of either tramadol or morphine (MOR agonist). It could be concluded that tramadol is capable to induced state-dependent memory and also, it has a cross state-dependent memory with morphine in the hippocampus, done possibly through MOR.
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