Pharmacology and Neurotoxicity of 5-MeO-DIPT
Handbook of Neurotoxicity January 1, 2021 Peer reviewed DOI: 10.1007/978-3-030-71519-9_207-1 via Springer Nature
Summary
5-MeO-DIPT, a psychedelic drug, was found to have significant effects on neurotransmitter release and cognitive performance in adolescent rats. Repeated exposure led to decreased dopamine, serotonin, and glutamate responses to subsequent doses, alongside oxidative DNA damage in the cortex. Additionally, cognitive impairments were noted, particularly in long-term memory and cognitive flexibility. These findings suggest potential long-term neurological issues due to adolescent exposure to 5-MeO-DIPT.
Study at a glance
| Population | adolescent rats |
|---|---|
| Key finding | Repeated-intermittent administration of 5-MeO-DIPT during adolescence impaired neurotransmitter responses and cognitive performance in rats. |
Abstract
Psychedelics are drugs that alter consciousness and affect human psyche. 5-Methoxy- N,N -diisopropyltryptamine (5-MeO-DIPT) emerged in the recreational drug market with the street name “foxy” and has been increasingly used as a substitute for methylenedioxymethamphetamine (MDMA) Methylenedioxymethamphetamine (MDMA) . 5-MeO-DIPT is a competitive inhibitor of the serotonin (5-HT) transporter (SERT), having lower affinity for the dopamine (DA) transporter (DAT) but with high affinity for 5-HT2A, 5-HT2C, and 5-HT1A receptors. As a 5-HT2A receptor agonist, 5-MeO-DIPT produces hallucinogenic effect in mice and rats and increases in vivo release of DA, 5-HT, and glutamate in rat striatum, nucleus accumbens, and frontal cortex. The potent cytotoxic effect of 5-MeO-DIPT was demonstrated in COS-7 cells and in SH-SY5Y and Hep G2 cell lines . Repeated-intermittent 5-MeO-DIPT administration (2.5 mg/kg × 8) in adolescence decreased response to a challenge dose of 5-MeO-DIPT in release of DA, 5-HT, and glutamate in some regions of the rat brain. Furthermore, oxidative DNA damage was observed in the rat cortex. In rats exposed to 5-MeO-DIPT during adolescence, response of DA, 5-HT, and glutamate neurons in the frontal cortex to a challenge dose of MDMA was stronger in comparison with the saline group. 5-MeO-DIPT disturbed animal performance in certain cognitive tasks, while exposure of adolescent rats to repeated-intermittent doses of 5-MeO-DIPT produced impairment of long-term memory or cognitive flexibility in the serial pattern learning test. Abnormalities seen after exposure to 5-MeO-DIPT during adolescence suggest that developmental changes may cause neurological problems in adult life.