Prelimbic cortex dynorphin/κ opioid receptor system modulates methamphetamine‐induced cognitive impairment

• Published in: Addiction biology Vol. 28; no. 9; pp. e13323 - n/a
• Main Authors: Cheng, Ying‐jie, Deng, Ying‐zhi, Deng, Di, Wu, Man‐qing, Chai, Jing‐rui, Wang, Yu‐jun, Liu, Jing‐gen, Zhao, Min
• Format: Journal Article
• Language: English
• Published: Leeds John Wiley & Sons, Inc 01.09.2023
• Subjects: Antagonists; Chronic exposure; Cognitive ability; cognitive impairment; Cortex; Drug abuse; Dynorphin; Methamphetamine; Microinjection; mRNA; Narcotics; Neuroprotection; Opioid receptors; Pattern recognition; prelimbic cortex; Spontaneous alternation; κ opioid receptor
• ISSN: 1355-6215; 1369-1600
• DOI: 10.1111/adb.13323

Chronic exposure to methamphetamine (METH) causes severe and persistent cognitive impairment. The present study aimed to investigate the role of dynorphin/κ opioid receptor (KOR) system in the development of METH‐induced cognitive impairment. We found that mice showed significant cognitive impairment in the novel object recognition test (NOR) following daily injections of METH (10 mg/kg) for seven consecutive days. Systemic blockade of KOR prevented METH‐induced cognitive impairment by pretreatment of the selective KOR antagonist norBNI (10 mg/kg, i.p.) or KOR deletion. Then, significant increased dynorphin and KOR mRNA were observed exclusively in prelimbic cortex (PL) other than infralimbic cortex. Finally, microinjection with norBNI into PL also improved cognitive memory in METH‐treated mice using NOR and spontaneous alternation behaviour test. Our results demonstrated that dynorphin/KOR system activation in PL may be a possible mechanism for METH‐induced cognitive impairment and shed light on KOR antagonists as a potential neuroprotective agent against the cognitive deficits induced by drug abuse. Blockade of κ opioid receptor (KOR) prevented METH‐induced cognitive impairment. Chronic METH administration increased dynorphin and KOR mRNA level in prelimbic cortex (PL) but not infralimbic cortex (IL). KOR antagonist injections into PL but not IL attenuated cognitive impairment after METH exposure.