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Open Access 01-01-2019 | Original Article

Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats

Authors: Karolina Noworyta-Sokołowska, Katarzyna Kamińska, Joanna Rzemieniec, Agnieszka Wnuk, Jakub Wojcieszak, Anna Maria Górska, Grzegorz Kreiner, Małgorzata Kajta, Krystyna Gołembiowska

Published in: Forensic Toxicology | Issue 1/2019

Abstract

Purpose

Tryptamine hallucinogen 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is a serotonin transporter inhibitor with high affinity for serotonin 5-HT_1A and 5-HT_2A/C receptors. We showed previously that 5-MeO-DIPT in a single dose increased neurotransmitter release in brain regions of rats and elicited single- and double-strand DNA breaks. Herein we investigated the effects of repeated-intermittent 5-MeO-DIPT administration in adolescence on dopamine (DA), serotonin (5-HT) and glutamate release in brain regions of adult rats. Furthermore, we examined caspase-3 activity, oxidative DNA damage, the Gpx3, Sod1, Ht1a and Ht2a mRNA expression levels, and cell viability.

Methods

Neurotransmitter release was measured by microdialysis in freely moving animals. Caspase-3 activity was assessed colorimetrically, and oxidative DNA damage with the comet assay, while the Gpx3, Sod1, Ht1a and Ht2a mRNA expression levels were assessed by real-time polymerase chain reaction. Cell viability was studied in SH-SY5Y and Hep G2 cells by the MTT test.

Results

We observed changed responses of DA, 5-HT and glutamate neurons to a challenge dose of 5-MeO-DIPT when animals were treated repeatedly in adolescence with this hallucinogen. The basal extracellular levels of DA and 5-HT were decreased in the striatum and nucleus accumbens, while glutamate level was increased in the nucleus accumbens and frontal cortex. The damage of cortical DNA, increased Gpx3 and Sod1 mRNA expression and affected caspase-3 activity were also observed. Furthermore, decreased Ht1a and Ht2a mRNA expression in the frontal cortex and marked cytotoxicity of 5-MeO-DIPT were found.

Conclusions

These results suggest that 5-MeO-DIPT given repeatedly during adolescence affects brain neurotransmission and shows neurotoxic potential observed in adult animals.

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Title: Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats
Authors: Karolina Noworyta-Sokołowska
Katarzyna Kamińska
Joanna Rzemieniec
Agnieszka Wnuk
Jakub Wojcieszak
Anna Maria Górska
Grzegorz Kreiner
Małgorzata Kajta
Krystyna Gołembiowska
Publication date: 01-01-2019
Publisher: Springer Singapore
Published in: Forensic Toxicology / Issue 1/2019
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-018-0433-x

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Effects of exposure to 5-MeO-DIPT during adolescence on brain neurotransmission and neurotoxicity in adult rats

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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