The Cdk5 inhibitor β‐butyrolactone impairs reconsolidation of heroin‐associated memory in the rat basolateral amygdala

Abstract

AbstractThe persistence of maladaptive heroin‐associated memory, which is triggered by drug‐related stimuli that remind the individual of the drug's pleasurable and rewarding effects, can impede abstinence efforts. Cyclin‐dependent kinase 5 (Cdk5), a neuronal serine/threonine protein kinase that plays a role in multiple neuronal functions, has been demonstrated to be involved in drug addiction and learning and memory. Here, we aimed to investigate the role of cdk5 activity in the basolateral amygdala (BLA) in relapse to heroin seeking, using a self‐administration rat model. Male rats underwent 10 days of heroin self‐administration training, during which an active nose poke resulted in an intravenous infusion of heroin that was accompanied by a cue. The rats then underwent nose poke extinction for 10 days, followed by subsequent tests of heroin‐seeking behaviour. We found that intra‐BLA infusion of β‐butyrolactone (100 ng/side), a Cdk5 inhibitor, administered 5 min after reactivation, led to a subsequent decrease in heroin‐seeking behaviour. Further experiments demonstrated that the effects of β‐butyrolactone are dependent on reactivated memories, temporal‐specific and long‐lasting on relapse of heroin‐associated memory. Results provide suggestive evidence that the activity of Cdk5 in BLA is critical for heroin‐associated memory and that the specific inhibitor, β‐butyrolactone, may hold potential as a substance for the treatment of heroin abuse.