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

Abstract Chronic exposure to methamphetamine (METH) causes severe and persistent cognitive impairment. The present study aimed investigate the role of dynorphin/κ opioid receptor (KOR) system in development METH‐induced We found that mice showed significant impairment novel object recognition test (NOR) following daily injections METH (10 mg/kg) for seven consecutive days. Systemic blockade KOR prevented by pretreatment selective antagonist norBNI mg/kg, i.p.) or deletion. Then, increased dynorphin mRNA were observed exclusively prelimbic cortex (PL) other than infralimbic cortex. Finally, microinjection with into PL also improved memory METH‐treated using NOR spontaneous alternation behaviour test. Our results demonstrated dynorphin/KOR activation may be a possible mechanism shed light on antagonists as potential neuroprotective agent against deficits induced drug abuse.