Journal of Molecular Neuroscience

, Volume 58, Issue 4, pp 446–455 | Cite as

CB1 Cannabinoid Agonist (WIN55,212-2) Within the Basolateral Amygdala Induced Sensitization to Morphine and Increased the Level of μ-Opioid Receptor and c-fos in the Nucleus Accumbens

  • Marzieh Molaei
  • Zahra Fatahi
  • Jalal Zaringhalam
  • Abbas HaghparastEmail author


The basolateral amygdala (BLA) is rich of CB1 cannabinoid receptors (CB1R) and has reciprocal connections with the nucleus accumbens (NAc) which is involved in opioid sensitization. In this study, effects of intra-BLA administration of CB1R agonist on sensitization to antinociceptive effect of morphine and changes in the levels of μ-opioid receptor (MOR), p-CREB, and c-fos in the NAc were investigated. Animals received intra-BLA microinjection of CB1R agonist (WIN55,212-2) once daily for 3 days consecutively (sensitization period). After 5 days free of drug, tail-flick test was performed before and after the administration of an ineffective dose of morphine. Afterward, the levels of MOR, p-CREB, and c-fos proteins were measured in the NAc by Western blot analysis. The results indicated that intra-BLA injection of WIN55,212-2 during sensitization period resulted in the induction of antinociceptive responses by ineffective dose of morphine and caused a significant increase in the MOR and c-fos levels but not p-CREB/CREB ratio in the NAc. These finding revealed that CB1 receptor agonist in the BLA induces development of morphine sensitization and increases expression of MOR in the NAc. It seems that c-fos is one of the important factors involved in the induction of sensitization to antinociceptive effect of morphine.


Morphine sensitization Basolateral amygdala CB1 cannabinoid receptor μ-Opioid receptor c-fos p-CREB 



This research was supported by the funding from the Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12031_2016_716_MOESM1_ESM.docx (35 kb)
ESM 1 (DOCX 34 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Marzieh Molaei
    • 1
  • Zahra Fatahi
    • 2
  • Jalal Zaringhalam
    • 3
  • Abbas Haghparast
    • 1
    Email author
  1. 1.Neuroscience Research CenterShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Neurobiology Research Center, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Neurophysiology Research Center, Faculty of MedicineShahid Beheshti University of Medical SciencesTehranIran

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