Abstract
Substance use disorders (SUDs) are ubiquitous throughout the world. However, much remains to be done to develop pharmacotherapies that are very efficacious because the focus has been mostly on using dopaminergic agents or opioid agonists. Herein we discuss the potential of using potassium channel activators in SUD treatment because evidence has accumulated to support a role of these channels in the effects of rewarding drugs. Potassium channels regulate neuronal action potential via effects on threshold, burst firing, and firing frequency. They are located in brain regions identified as important for the behavioral responses to rewarding drugs. In addition, their expression profiles are influenced by administration of rewarding substances. Genetic studies have also implicated variants in genes that encode potassium channels. Importantly, administration of potassium agonists have been shown to reduce alcohol intake and to augment the behavioral effects of opioid drugs. Potassium channel expression is also increased in animals with reduced intake of methamphetamine. Together, these results support the idea of further investing in studies that focus on elucidating the role of potassium channels as targets for therapeutic interventions against SUDs.
Highlights
Substance use disorders (SUDs) are biopsychosocial disorders include neuropsychiatric symptoms such as loss of control of drug taking, repeated relapses to drug taking after intervals of forced or voluntary abstinence, and continued drug use in the presence of adverse consequences as described in the Diagnostic Statistical Manual of the American Psychiatric Association [1]
Chronic intermittent ethanol (CIE) exposure influenced the expression of Kcnb1, Kcnc2, Kcnc4, Kcnd2, and Kcnv1 whereas heavy alcohol use impacted Kcna4, Kcnh2, Kcnh7, Kcnq1, Kcnq5, Kcns1, Kcns2, and Kcnv2 expression (Table 2) [68]
We investigated the expression of calcium-activated K+ channels in animals that had received saline or METH prior to being put through the METH self-administration (METH SA) experiments [53]
Summary
Substance use disorders (SUDs) are biopsychosocial disorders include neuropsychiatric symptoms such as loss of control of drug taking, repeated relapses to drug taking after intervals of forced or voluntary abstinence, and continued drug use in the presence of adverse consequences as described in the Diagnostic Statistical Manual of the American Psychiatric Association [1]. Classification of Potassium Channels Ion channels are integral pore-forming transmembrane proteins that selectively control the influx and efflux of important physiological ions including Na+, K+, Ca2+, and Cl− into and from cells or intracellular organelles. They serve to control cytoplasmic and intraorganellar concentrations of these ions as well as regulate membrane potential and cell volume. Ninety identified K+ channels have been divided into subgroups based on their molecular structures and mechanisms of activation [12,13] These include (1) voltage-gated (KV), (2) calcium-activated (KCa), (3) two/tandem-pore domain (K2P) subgroup, (4) inwardly rectifying (KIR) subgroup. Detailed effects of these drugs on potassium channels are described below
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