Abstract
Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP) can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support MAP as a model for schizophrenia.
Highlights
Methamphetamine is a lipophilic compound used recreationally for its ability to temporarily induce a variety of desirable effects, including increased energy levels, positive mood, euphoria, reduced appetite, weight loss, enhanced mental acuity, social, and sexual disinhibition (Cretzmeyer et al, 2003; Green and Halkitis, 2006; Cruickshank and Dyer, 2009).According to the United Nations World Drug Report, between 0.3 and 1.3% of the world’s population uses amphetaminetype stimulants (United Nations Office, 2011; Burns, 2014)
Emerging evidence that will be discussed in this paper suggests that the cognitive deficits in Methamphetamine induced psychosis (MAP) may result from a GABAergic dysfunction in the cortex, the mechanism for these observations are unknown
We propose a possible vulnerability of GABAergic interneurons in the cortex to glutamate overflow, which might explain the GABAergic disturbance by methamphetamine that might lead to psychosis
Summary
Methamphetamine is a lipophilic compound used recreationally for its ability to temporarily induce a variety of desirable effects, including increased energy levels, positive mood, euphoria, reduced appetite, weight loss, enhanced mental acuity, social, and sexual disinhibition (Cretzmeyer et al, 2003; Green and Halkitis, 2006; Cruickshank and Dyer, 2009). Most relevant to this review is the methamphetamine sensitization model, where lower doses of repeated methamphetamine exposure have been shown to produce behavioral effects that best model psychosis by measurements such as increased locomotion, hallucinatory behaviors in the case of non-human primates, and deficits in pre-pulse inhibition, latent inhibition, and other cognitive measures in a variety of animal models (Castner and Goldman-Rakic, 1999; Kamei et al, 2006; Featherstone et al, 2007; Nagai et al, 2007; Forrest et al, 2014). We propose a possible vulnerability of GABAergic interneurons in the cortex to glutamate overflow, which might explain the GABAergic disturbance by methamphetamine that might lead to psychosis
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