title: Neurotoxic Effects of 5-MeO-DIPT: A Psychoactive Tryptamine Derivative in Rats.
abstract: 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.
authors.affiliation: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Noworyta-Sokołowska
authors.affiliation: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kamińska
authors.affiliation: Department of Biochemistry, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kreiner
authors.affiliation: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Rogóż
authors.affiliation: Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland. nfgolemb@cyf-kr.edu.pl.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Gołembiowska
mesh_terms: D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000633:toxicity; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity*; D013287:Illicit Drugs / Q000633:toxicity; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism
chemical_list: D000662:Amphetamines; D006213:Hallucinogens; D013287:Illicit Drugs; C033696:5-methoxy-N,N-diisopropyltryptamine; D012701:Serotonin; D018698:Glutamic Acid; D008735:5-Methoxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine
keywords: 5-HT; 5-MeO-DIPT; DA; DNA damage; Glutamate in brain regions; Head twitch; Playing piano; Toxicity