Abstract
Abuse of amphetamine-type stimulants (ATS) has become a global public health problem. ATS causes severe neurotoxicity, which could lead to addiction and could induce psychotic disorders or cognitive dysfunctions. However, until now, there has been a lack of effective medicines for treating ATS-related problems. Findings from recent studies indicate that in addition to the traditional dopamine-ergic system, the GABA (gamma-aminobutyric acid)-ergic system plays an important role in ATS abuse. However, the exact mechanisms of the GABA-ergic system in amphetamine-type stimulant use disorders are not fully understood. This review discusses the role of the GABA-ergic system in ATS use disorders, including ATS induced psychotic disorders and cognitive dysfunctions. We conclude that the GABA-ergic system are importantly involved in the development of ATS use disorders through multiple pathways, and that therapies or medicines that target specific members of the GABA-ergic system may be novel effective interventions for the treatment of ATS use disorders.
Highlights
Abuse of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyamphetamine (MDA), is a global public health problem
The mechanism could be that the activation of GABAA receptor decreases dopaminergic neurotransmission, which could be increased by inhibition of GABAA receptor, suggesting that GABAAreceptors may play an inhibitory role in ATS use disorders
Their results showed that the NPYGAD1TG mice displayed a significantly greater increase of up to a 600% peak response to amphetamine compared with the littermate controls
Summary
Abuse of amphetamine-type stimulants (ATS), including amphetamine, methamphetamine (METH), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyamphetamine (MDA), is a global public health problem. The prevalence of psychosis in methamphetamine abusers ranges between 10 and 60% (Farrell et al, 2002; McKetin et al, 2006; Mahoney et al, 2008) Various animal behaviors, such as increased activation and hallucinogenesis in non-human primates (Castner and Goldman-Rakic, 1999), and increased locomotion activity, stereotyped behavior, deficits in prepulse inhibition and latent inhibition, or. Emerging evidence that will be discussed in this paper suggests that a GABA-ergic dysfunction may result in ATS use disorders, including ATS-induced psychiatric disorders and cognitive dysfunction. We further discuss addiction-related brain regions in ATS use disorders, such the prefrontal cortex, striatum, and the involvement of GABA system in the dysfunctions of these neural circuits. This review summarizes the involvement of GABA-ergic system in ATS use disorders, providing us with a new aspect on research on ATS use disorders
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