Altered Activity of SK Channel Underpins Morphine Withdrawal Relevant Psychiatric Deficiency in Infralimbic to Accumbens Shell Pathway

In this study, we investigated the role of the small conductance calcium-activated potassium channels (SK channels) in NAc and mPFC after morphine withdrawal. Action potential (AP) firing of neurons in the NAc shell was enhanced via the downregulations of the SK channels after morphine withdrawal. Furthermore, the expression of SK2 and SK3 subunits in the NAc was significantly reduced after 3 weeks of morphine withdrawal, but was not altered in the dorsal striatum. In mPFC, the SK channel subunits were differentially expressed. To be specific, the expression of SK3 was upregulated, while the expression of SK2 was unchanged. Furthermore, the AP firing in layer 5 pyramidal neurons of the infralimbic (IL) cortex was decreased via the upregulations of the SK channel-related tail current after 3 weeks of morphine withdrawal. These results suggest that the SK channel plays a specific role in reward circuits following morphine exposure and a period of drug withdrawal, making it a potential target for the prevention of relapse.IntroductionDrug addiction can be viewed as a mental health disorder caused by maladaptive neural plasticity (1). It involves long-term and persistent dysregulation of neural circuits, particularly in motivational systems and reward systems (2). Opioids, including morphine, are the first-line choice for the management of chronic pain and moderate-to-severe acute pain in both cancer and noncancer patients (3). However, repeated morphine exposure can lead to addi...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research