Abstract
Ethanol can induce acute stimulant responses in animals and human beings. Moreover, repeated exposure to ethanol may produce increased sensitivity to its acute locomotor stimulant actions, a process referred to as locomotor sensitization. The molecular mechanism of the development of acute stimulant responses and locomotor sensitization by ethanol is not fully understood. Sodium leak channel (NALCN) is widely expressed in central nervous system and controls the basal excitability of neurons. The present study aims to determine whether NALCN is implicated in the ethanol-induced acute responses and locomotor sensitization in mice. Here, our results showed that ethanol caused acute stimulant responses in DBA/2 mice. Locomotor sensitization was successfully induced following the sensitization procedure. Accordingly, the expression levels of NALCN mRNA and protein in the nucleus accumbens (NAc) were markedly increased in the sensitization mice compared to the control mice. Knockdown the expression levels of NALCN in the NAc alleviated both the ethanol-induced acute responses and locomotor sensitization. Our findings indicate that upregulation of NALCN expression in the NAc contributes to the ethanol-induced acute stimulant responses and locomotor sensitization in DBA/2 mice.
Highlights
Ethanol is one of the most commonly abused substances (Abrahao et al, 2017)
NALCN is widely expressed in the central nervous system and regulates neuronal excitability (Lu et al, 2007)
The present study demonstrates that NALCN in nucleus accumbens (NAc) can modulate the ethanol-induced acute stimulant responses and chronic locomotor sensitization in DBA/2 mice
Summary
Ethanol is one of the most commonly abused substances (Abrahao et al, 2017). environmental and genetic factors were believed to contribute to the etiology of alcohol use disorders (AUD), the molecular bases of ethanol’s actions was not fully known, including acute stimulant responses and chronic changes in behavior, such as escalated use, compulsive seeking, tolerance, and dependence (Abrahao et al, 2017). Repeated exposure to ethanol will cause locomotor sensitization, which is a defining. NALCN in Ethanol Actions characteristic of AUD, as displayed by increased sensitivity to the acute locomotor stimulant actions of ethanol after repeated administrations (Robinson and Berridge, 1993). Animal models of locomotor sensitization have been commonly used to assess motivational salience induced by repeated exposure to drugs of abuse, including ethanol (Abrahao et al, 2013; Coelhoso et al, 2013). The molecular mechanism of the development of both ethanol-induced acute responses and locomotor sensitization remains unclear. Many studies have highlighted the importance of NAc in regulating the process of drug-induced locomotor sensitization, such as methamphetamine and ethanol (Rose et al, 2013; Su et al, 2019; Ferreira et al, 2021; Porru et al, 2021)
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