当前位置： SCI文献检索 > NEUROSCIENCE LETTERS期刊下所有文献 > Heroin-based crack induces hyperalgesia through β-arrestin 2 redistribution and phosphorylation of Erk1/2 and JNK in the periaqueductal gray area.

Heroin-based crack induces hyperalgesia through β-arrestin 2 redistribution and phosphorylation of Erk1/2 and JNK in the periaqueductal gray area.

Abstract：

:Continuous use of crack induces hyperalgesia which is related to drug tolerance. Despite cumulative evidence based on the growth rate of crack abuse, no serious study has been focused on the mechanisms of crack-induced hyperalgesia. This study aimed to elucidate whether extracellular signal-regulated kinases (Erk1/2)/β-arrestin pathways are involved in the crack-induced hyperalgesia. Fifty adult male Wistar rats were randomly divided into five groups: normal saline (NS), crack (0.9 mg/kg/day), heroin (1 mg/kg/day), crack + barbadin (100 μM), and heroin + barbadin groups, which received their intraperitoneal (i.p) treatments for four weeks. The thermal sensitivity was assessed using the hot-plate test. Moreover, phosphorylation of the Erk1/2 and JNK, as well as expression of protein kinase C-alpha (PKC-α), Mu-receptor (MOR), and β-arrestin 2 were determined in the whole lysate and membrane fraction using immunoblotting assay in the periaqueductal gray (PAG) area. The results demonstrated that chronic administration of crack and heroin significantly decreased hind-paw withdrawal latency compared to the NS group. Furthermore, crack as well as heroin administration increased phosphorylated Erk1/2 and JNK in the PAG. In addition, membrane β-arrestin 2 and PKC-α were significantly increased in the crack and heroin-received groups, while membrane MOR expression was decreased in the PAG. Nevertheless, co-administration of barbadin, an inhibitor of β-arrestin, and crack or heroin reversed all these changes. Our findings may partially confirm the role of β-arrestin 2 and PKC rearrangements, Erk1/2 and JNK phosphorylation in crack-induced hyperalgesia and provide potential therapeutic targets to attenuate crack-induced hyperalgesia.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Aberoumandi SM,Vousooghi N,Tabrizi BA,Karimi P

doi

10.1016/j.neulet.2019.01.023

subject

Has Abstract

pub_date

2019-04-17 00:00:00

pages

133-139

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(19)30029-1

journal_volume

698

pub_type

杂志文章

在线工具

Heroin-based crack induces hyperalgesia through β-arrestin 2 redistribution and phosphorylation of Erk1/2 and JNK in the periaqueductal gray area.