The involvement of ventral hippocampal microglial cells, but not cannabinoid CB1 receptors, in morphine-induced analgesia in rats

  • Hanieh Javid
  • Ameneh RezayofEmail author
  • Zahra Ghasemzadeh
  • Maryam Sardari
Original article


It is well known that glial cells are involved in pain processing. The purpose of the present study was to investigate the possible involvement of the ventral hippocampal (VH) glial cells in morphine-induced analgesia. A tail-flick apparatus was used to measure pain sensitivity in male Wistar rats that were bilaterally cannulated in the VH by stereotaxic surgery. The results showed that intraperitoneal (i.p.) administration of morphine (2.5–7.5 mg/kg) induced analgesia in a time-dependent manner. The blockade of the VH glial cell activation by bilateral microinjection of a glial inhibitor, minocycline (5–15 µg/rat) into the VH with an ineffective dose of morphine (2.5 mg/kg, i.p) significantly increased morphine analgesia. Considering that the endocannabinoid system via CB1 receptors play a crucial role in pain modulation, we also assessed the possible role of the VH cannabinoid CB1 receptors in the functional interaction between minocycline and morphine in acute pain. Our results indicated that intra-VH injection of the cannabinoid CB1 receptor agonist, arachidonylcyclopropylamide (ACPA; 4–12 ng/rat) had no effect on minocycline-induced potentiation of morphine analgesia. It should be considered that intra-VH microinjection of minocycline or ACPA by itself had no effect on tail-flick latency. Our findings suggest that the activation of the VH microglial cells may be involved in mediating pain sensation, because the inhibition of these cells by intra-VH injection of minocycline could potentiate morphine-induced analgesia. Although endocannabinoids have a regulatory role in glia function, the activation of CB1 receptors could not affect the potentiative effect of minocycline on morphine analgesia.


Morphine Minocycline ACPA Ventral hippocampus Analgesia Rat(s) 





Analysis of variance


Area under the curve








Long-term potentiation


Mitogen-associated protein kinases


Maximum possible effect


Standard error of mean


Tail-flick latency


Ventral hippocampus


WIN55,212-2 mesylate


Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.


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Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  • Hanieh Javid
    • 1
  • Ameneh Rezayof
    • 1
    Email author
  • Zahra Ghasemzadeh
    • 1
  • Maryam Sardari
    • 1
  1. 1.Department of Animal Biology, School of Biology, College of ScienceUniversity of TehranTehranIran

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