Abstract
Methamphetamine is a potent addictive stimulant drug that activates certain systems in the brain. It is a member of the amphetamine family, but the effects of methamphetamine are much more potent, longer lasting, and more harmful to the central nervous system. Repeated administration of methamphetamine induces behavioral sensitization, which is considered to be related to compulsive drug-seeking behavior. Although the mechanism responsible for methamphetamine-induced behavioral sensitization remains unclear, it is believed that the mesolimbic dopaminergic system in the central nervous system plays a critical role in the development of behavioral sensitization. Our previous studies indicate that the involvement of the μ-opioid receptor system underlies the development of methamphetamine-induced behavioral sensitization. Understanding the mechanisms of behavioral sensitization that are regulated by the μ-opioid receptor system would be helpful in developing therapeutic programs against methamphetamine addiction. This review briefly discusses the neural circuitry and cellular mechanisms that are known to play a central role in methamphetamine-induced behavioral sensitization and outlines the role of the μ-opioid receptor system in the development of methamphetamine-induced sensitization.
Highlights
Methamphetamine is a central nervous system stimulant drug that is similar in structure to amphetamine but has a higher potential for abuse, resulting in behavioral changes including sensitization, tolerance, and dependence [1]
Previous studies have indicated that once sensitization has developed, a challenge dose of methamphetamine resulted in behavioral hyperactivity, characterized by increase in locomotor activity and stereotyped behaviors in mice [14, 21]
The mechanism responsible for methamphetamine-induced behavioral sensitization remains unclear, it is believed that the mesolimbic dopaminergic system in the central nervous system plays a critical role in the development of behavioral sensitization [4, 22, 23]
Summary
Methamphetamine is a central nervous system stimulant drug that is similar in structure to amphetamine but has a higher potential for abuse, resulting in behavioral changes including sensitization, tolerance, and dependence [1]. Our previous studies have shown that blockade of the μ-opioid receptor caused reduced development of methamphetamine-induced sensitization [14,15,16] and that these results were related to the changes in the levels of dopamine and its metabolites [17], as well as to the binding of dopamine receptors [18].
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