• Zahra Ghasemzadeh and Ameneh Rezayof.
• Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
• Neuroscience. 2018 Nov 21; 393: 295-304.

AbstractThe present study set out to assess the possible role of the medial prefrontal cortex (mPFC) cannabinoid CB1 receptors and BDNF/cFOS signaling pathways in morphine-dextromethorphan (DXM) cross state-dependent memory (SDM) using male Wistar rats. Changes on the levels of BDNF and cFOS proteins in the PFC were examined by Western blot analysis. Present results revealed that levels of BDNF and cFOS proteins were significantly increased in the animals that were trained in the passive avoidance apparatus. Intraperitoneal injection of morphine (6 mg/kg, i.p.) after training impaired memory which was associated with decreases in the levels of both proteins. Moreover, the injection of a cannabinoid CB1 receptor agonist, ACPA, or a selective CB1 receptor antagonist, AM-251, into the mPFC prior to testing had no effect on memory retrieval by itself and also on morphine-induced memory loss. Pre-test administration of DXM (a NMDA receptors antagonist, 30 mg/kg, i.p.) impaired memory retrieval and attenuated BDNF levels. Moreover, DXM administration (pre-test) prevented morphine-induced memory loss and increased the levels of both proteins, suggesting morphine-DXM cross-SDM. Interestingly, pre-test intra-mPFC injections of ACPA inhibited cross-SDM between the drugs which was associated with an elevation of BDNF expression in the PFC. Additionally, pre-test administration of an ineffective dose of DXM (10 mg/kg, i.p.) could not reverse morphine-induced memory loss, while pre-test intra-mPFC injections of AM-251 potentiated morphine-DXM cross-SDM. Taken together, it can be concluded that mPFC through CB1cannabinoid receptors has a critical role in morphine-DXM cross-SDM which may be associated with the PFC BDNF/cFOS signaling pathway.Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

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