Minocycline alleviates the symptoms of morphine withdrawal via the CaMKII-Ras-ERK signaling pathway

Qiaofeng Liu; Ting Min; Jun Dong; Xin Wang

doi:10.1016/j.neulet.2021.135825

Minocycline alleviates the symptoms of morphine withdrawal via the CaMKII-Ras-ERK signaling pathway

Neurosci Lett. 2021 May 1:752:135825. doi: 10.1016/j.neulet.2021.135825. Epub 2021 Mar 13.

Authors

Qiaofeng Liu¹, Ting Min¹, Jun Dong¹, Xin Wang²

Affiliations

¹ Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, China; Department of Pathogenic Biology, Chengdu Medical College, Chengdu, China.
² Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu, China; Department of Pathogenic Biology, Chengdu Medical College, Chengdu, China. Electronic address: 407434194@qq.com.

PMID: 33727130
DOI: 10.1016/j.neulet.2021.135825

Abstract

Objective: To investigate the effect of minocycline on morphine withdrawal symptoms.

Methods: We established a rat model of morphine dependence, then injected the animals with naloxone to induce withdrawal symptoms. Minocycline was injected into the midbrain periaqueductal gray and its effect on withdrawal symptoms and Ca²⁺-dependent protein kinase (CaMKII), Ras, and phospho-extracellular signal-regulated kinase (p-ERK) expression was observed.

Results: Minocycline inhibited withdrawal symptoms such as "wet dog" shakes, teeth chatter, and ptosis, perhaps by inhibiting the activation of microglia and the expression of CaMKII, Ras, and p-ERK. Minocycline had no effect on the behavior of control rats or on CaMKII, Ras, or p-ERK expression.

Conclusion: Minocycline alleviates morphine withdrawal symptoms by inhibiting the activation of microglia and downregulating the expression of CaMKII, Ras, and p-ERK.

Keywords: CaMKII; Midbrain periaqueductal gray; Minocycline; Morphine withdrawal; Ras; p-ERK.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Disease Models, Animal
Down-Regulation / drug effects
Humans
MAP Kinase Signaling System / drug effects*
Male
Microglia / drug effects
Microglia / pathology
Minocycline / pharmacology*
Minocycline / therapeutic use
Morphine / adverse effects*
Morphine / antagonists & inhibitors
Naloxone / administration & dosage
Periaqueductal Gray / drug effects
Periaqueductal Gray / pathology
Rats
Substance Withdrawal Syndrome / drug therapy*
Substance Withdrawal Syndrome / pathology
ras Proteins / metabolism

Substances

Naloxone
Morphine
Calcium-Calmodulin-Dependent Protein Kinase Type 2
ras Proteins
Minocycline