Role of dorsal hippocampal orexin-1 receptors in memory restoration induced by morphine sensitization phenomenon

• Pre-training administration of morphine impaired memory acquisition/retrieval in MWM.
• Amnesia induced by morphine inhibited in morphine-sensitized rats.
• Repeated or acute intra-CA1 injection of SB-334867 did not alter morphine-induced amnesia.
• Repeated CA1 OX1Rs blockade had no effect on memory in morphine-sensitized rats.
• SB-334867 injection in the expression phase disrupted memory induced by morphine sensitization.

The present study was examined the blockade of CA1 orexin-1 receptors (OX1Rs) of the dorsal hippocampus in the induction or expression phase on morphine sensitization-induced memory restoration using the Morris water maze (MWM) apparatus. Results showed that pre-training administration of morphine (5 mg/kg, s.c.) increases escape latency and traveled distance, while does not alter swimming speed. This supports the impairing effect of morphine on the spatial memory acquisition in male adult rats. Also, in the retrieval session (probe trial) this treatment decreased the time spent in the target quadrant. Moreover, morphine-induced sensitization (15 or 20 mg/kg, s.c.; once daily for 3 days and followed by 5 days no drug treatment) restored the memory acquisition/retrieval deficit which had been induced by pre-training administration of morphine (5 mg/kg, s.c.). Intra-CA1 microinjection of subthreshold doses of SB-334867 (OX1Rs antagonist; 10, 20 and 40 nmol/rat), 5 min before morphine (20 mg/kg/day × 3 days, s.c.; induction phase for morphine sensitization) did not alter restoration of memory acquisition/retrieval produced by the morphine sensitization phenomenon. In contrast, microinjection of subthreshold doses of SB-334867 (10, 20 and 40 nmol/rat) into the CA1 region in the training session, 5 min prior to morphine (5 mg/kg, s.c.; expression phase for morphine sensitization) blocked the spatial memory acquisition/retrieval in morphine-sensitized rats. In conclusion, these findings show that morphine sensitization reverses morphine-induced amnesia. Furthermore, the blockade of CA1 OX1Rs in the expression phase, but not in the induction phase, disrupts memory restoration induced by morphine sensitization.