Abstract
Repeated exposure to cocaine upregulates endoplasmic reticulum (ER) stress response and c-Jun N-terminal kinase (JNK) phosphorylation is associated with the ER stress response in neurons. In this study, we investigated the involvement of JNK in the regulation of the ER stress response following repeated cocaine administration in the dorsal striatum in vivo. The results showed that systemic injections of cocaine (20 mg/kg) for seven consecutive days increased the induction of p46 JNK (JNK) phosphorylation, immunoglobulin heavy chain binding protein (BiP), the ER stress-associated protein caspase-12, and behavioral locomotor activity. This enhancement of BiP and caspase-12 expression and locomotor response was reduced by inhibiting JNK. Similar reduction of elevated JNK phosphorylation was induced by blocking dopamine D1 receptors, N-methyl-D-aspartate (NMDA) receptors, and group I metabotropic glutamate receptors (mGluRs). These data suggest that JNK activation following repeated cocaine administration is required for the regulation of the ER stress protein expression and behavioral alteration in the dorsal striatum. Stimulation of dopamine D1 receptors, NMDA receptors or group I mGluRs participates in the regulation of JNK activation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.