Dataset Information

Effects of low-doses of methamphetamine on d-fenfluramine-induced head-twitch response (HTR) in mice during ageing and c-fos expression in the prefrontal cortex.

ABSTRACT:

Background

The head-twitch response (HTR) in mice is considered a behavioral model for hallucinogens and serotonin 5-HT_2A receptor function, as well as Tourette syndrome in humans. It is mediated by 5-HT_2A receptor agonists such as ( ±)- 2,5-dimethoxy-4-iodoamphetamine (DOI) in the prefrontal cortex (PFC). The 5-HT_2A antagonist EMD 281014, can prevent both DOI-induced HTR during ageing and c-fos expression in different regions of PFC. Moreover, the nonselective monoamine releaser methamphetamine (MA) suppressed DOI-induced HTR through ageing via concomitant activation of inhibitory 5-HT_1A receptors, but enhanced DOI-evoked c-fos expression. d-Fenfluramine is a selective 5-HT releaser and induces HTR in mice, whereas MA does not. Currently, we investigated whether EMD 281014 or MA would alter: (1) d-fenfluramine-induced HTR frequency in 20-, 30- and 60-day old mice, (2) d-fenfluramine-evoked c-fos expression in PFC, and (3) whether blockade of inhibitory serotonergic 5-HT_1A- or adrenergic ɑ₂-receptors would prevent suppressive effect of MA on d-fenfluramine-induced HTR.

Results

EMD 281014 (0.001-0.05 mg/kg) or MA (0.1-5 mg/kg) blocked d-fenfluramine-induced HTR dose-dependently during ageing. The 5-HT_1A antagonist WAY 100635 countered the inhibitory effect of MA on d-fenfluramine-induced HTR in 30-day old mice, whereas the adrenergic ɑ₂ antagonist RS 79948 reversed MA's inhibitory effect in both 20- and 30- day old mice. d-Fenfluramine significantly increased c-fos expressions in PFC regions. MA (1 mg/kg) pretreatment significantly increased d-fenfluramine-evoked c-fos expression in different regions of PFC. EMD 281014 (0.05 mg/kg) failed to prevent d-fenfluramine-induced c-fos expression, but significantly increased it in one PFC region (PrL at - 2.68 mm).

Conclusion

EMD 281014 suppressed d-fenfluramine-induced HTR but failed to prevent d-fenfluramine-evoked c-fos expression which suggest involvement of additional serotonergic receptors in the mediation of evoked c-fos. The suppressive effect of MA on d-fenfluramine-evoked HTR is due to well-recognized functional interactions between stimulatory 5-HT_2A- and the inhibitory 5-HT_1A- and ɑ₂-receptors. MA-evoked increases in c-fos expression in PFC regions are due to the activation of diverse monoaminergic receptors through increased synaptic concentrations of 5-HT, NE and/or DA, which may also account for the additive effect of MA on d-fenfluramine-evoked changes in c-fos expression. Our findings suggest potential drug receptor functional interaction during development when used in combination.

SUBMITTER: Sun Y

PROVIDER: S-EPMC9835290 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Effects of low-doses of methamphetamine on d-fenfluramine-induced head-twitch response (HTR) in mice during ageing and c-fos expression in the prefrontal cortex.

Sun Yina Y Chebolu Seetha S Skegrud Stone S Kamali Setareh S Darmani Nissar A NA

BMC neuroscience 20230111 1

<h4>Background</h4>The head-twitch response (HTR) in mice is considered a behavioral model for hallucinogens and serotonin 5-HT<sub>2A</sub> receptor function, as well as Tourette syndrome in humans. It is mediated by 5-HT<sub>2A</sub> receptor agonists such as ( ±)- 2,5-dimethoxy-4-iodoamphetamine (DOI) in the prefrontal cortex (PFC). The 5-HT<sub>2A</sub> antagonist EMD 281014, can prevent both DOI-induced HTR during ageing and c-fos expression in different regions of PFC. Moreover, the nonsel ...[more]

PMID: 36631757

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Dataset Information

Effects of low-doses of methamphetamine on d-fenfluramine-induced head-twitch response (HTR) in mice during ageing and c-fos expression in the prefrontal cortex.

Background

Results

Conclusion

Publications

Effects of low-doses of methamphetamine on d-fenfluramine-induced head-twitch response (HTR) in mice during ageing and c-fos expression in the prefrontal cortex.

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