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Pharmacol Biochem Behav. 2015 Jun;133:92-8. doi: 10.1016/j.pbb.2015.03.018. Epub 2015 Apr 3.

Influence of morphine on medial prefrontal cortex alpha2 adrenergic system in passive avoidance learning in rats.

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Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
Faculty of Pharmacy, Azad University, Tehran, Iran.
Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Institute for Studies in Theoretical Physics and Mathematics, School of Cognitive Sciences (IPM), Tehran, Iran; Institute of Cognitive Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran, Iran.


The prelimbic region of the medial prefrontal cortex (mPFC) is a brain area crucial for memory, attention, and decision making. It has been shown that α2-adreneoceptors (α2-ARs) play a powerful role in regulating memory and attention functions in this region. Since many studies have demonstrated the impairment effect of morphine on memory through mPFC, we aimed to investigate the possible interaction between α2-ARs of the mPFC and morphine induced amnesia in passive avoidance learning in rats. Animals were bilaterally implanted with chronic cannulas in the mPFC, trained in the step-through type passive avoidance task, and tested 24h after training; step-through latencies were measured. Our data indicate that post-training i.p. administration of morphine (2.5, 5 and 7.5mg/kg) dose-dependently reduced the step-through latency, showing an amnesic effect. Post-training intra-mPFC administration of yohimbine (an α2-adrenergic antagonist, 0.125, 0.25 and 0.5μg/rat) and clonidine (an α2-adrenergic agonist, 0.001, 0.01 and 0.2μg/rat), dose dependently impaired memory retrieval. Furthermore, post-training intra-mPFC microinjection of ineffective doses of yohimbine or clonidine significantly reversed the inhibitory effect of morphine on memory retrieval. Furthermore, SKF96365 (a presynaptic calcium channel blocker) reduced yohimbine and showed slight inhibition of clonidine effect. These results suggest that α2-ARs of the mPFC may play an important role in morphine-induced amnesia.


Alpha-2 adrenoceptor; Morphine; Passive avoidance learning; Prefrontal cortex; Rat(s)

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