The 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.