PKC inhibitor reversed the suppressive effect of orexin-A on IPSCs of locus coeruleus neurons in naloxone-induced morphine withdrawal

  • Mahnaz Davoudi
  • Kamini Vijeepallam
  • Hossein AziziEmail author
  • Javad Mirnajafi-Zadeh
  • Saeed SemnanianEmail author
Neurology and Preclinical Neurological Studies - Original Article


The locus coeruleus (LC) as a target of addictive drugs receives a dense projection of orexinergic fibres from the lateral hypothalamus (LH) and is accordingly a candidate site for the expression of the somatic aspects of morphine withdrawal. Recently it has been shown that the inhibitory synaptic currents of LC neurons decrease partly through orexin type 1 receptors in the context of naloxone-induced morphine withdrawal; however, its cellular mechanism remains unclear. In this study, whole-cell patch clamp recordings of LC neurons in brainstem slices were used to investigate the impact of protein kinase C (PKC) on GABAergic inhibitory post-synaptic currents (IPSCs) in the context of naloxone-induced morphine withdrawal. Male Wistar rats (P14–P21) received morphine (20 mg/kg, i.p.) daily for 7 consecutive days to induce morphine dependency. Our results showed that the application of PKC inhibitor (Go 6983; 1 µM) alone did not decrease the probability of GABA release in the LC neurons of the morphine-treated rats in the presence of naloxone. Although, Go 6983 reversed the reduction of the amplitude of evoked IPSCs (eIPSCs) and spontaneous IPSCs (sIPSCs) frequency induced by orexin-A but did not change the sIPSCs amplitude. These results indicate that the suppressive effect of orexin-A on IPSCs is probably reversed by PKC inhibitor in the LC neurons of morphine-treated rats in the context of naloxone withdrawal.


Locus coeruleus Naloxone-induced morphine withdrawal PKC inhibitor Orexin type 1 receptor GABAA-IPSCs 



This study was funded by the Cognitive Sciences and Technologies Council of Iran (CSTC, Grant no. 95P31), Iran National Science Foundation (INSF) and the Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Authors also wish to thank Dr. Amir Shojaei for his technical help. The authors would like to acknowledge Dr. Soomaayeh Heysieattalab and Mona Rahdar for helpful comments on the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.


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© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Physiology, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  2. 2.Department of Pharmacology, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia

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