Investigating the role of serotonin in methamphetamine psychosis: unaltered behavioral effects of chronic methamphetamine in 5-HT1A knockout mice

Jaehne, Emily J., Ameti, Dzeneta, Paiva, Tehani, and van den Buuse, Maarten (2017) Investigating the role of serotonin in methamphetamine psychosis: unaltered behavioral effects of chronic methamphetamine in 5-HT1A knockout mice. Frontiers in Psychiatry, 8. 61.

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Methamphetamine (Meth) is a widely abused stimulant drug, but this abuse is associated with an increased risk of developing psychosis. In addition to its well-known action on brain dopamine, Meth also affects serotonergic (5-HT) neurons. The aim of this study was to investigate this role in mice, which lack one of the main serotonin receptors, the 5-HT1A receptor, which has been implicated in both schizophrenia and Meth-induced psychosis. Male and female wild-type or 5-HT1A knockout (KO) mice received daily treatment with increasing doses of methamphetamine from 6 to 9 weeks of age (1-4 mg/kg/ day twice a day). At least 2 weeks after the last injection, the mice underwent a battery of behavioral tests focusing on psychosis-related behaviors, including Meth-induced hyperactivity, prepulse inhibition (PPI), social interaction, elevated plus maze (EPM), and Y-maze. Meth pretreatment resulted in significantly increased hyperlocomotion in response to an acute Meth challenge, but this effect was independent of genotype. Chronic Meth treatment resulted in decreased levels of anxiety in the EPM in both sexes, as well as increased startle responses in female mice only, again independent of genotype. 5-HT1A KO mice showed an increased locomotor response to acute Meth in both sexes, as well as increased PPI and decreased startle responses in female mice only, independent of Meth pretreatment. In conclusion, the effects of chronic Meth appear unaffected by the absence of the 5-HT1A receptor. These results do not support a role of the 5-HT1A receptor in Meth-induced psychosis.

Item ID: 50694
Item Type: Article (Research - C1)
ISSN: 1664-0640
Keywords: methamphetamine, psychosis, serotonin, 5-HT1A, receptors, neuroplasticity
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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC Senior Research Fellowship grant number 1041895
Date Deposited: 20 Sep 2017 11:06
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3205 Medical biochemistry and metabolomics > 320599 Medical biochemistry and metabolomics not elsewhere classified @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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