Abstract
4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a new psychoactive substance with strong hallucinogenic properties. Our previous data reported increased release of dopamine, serotonin, and glutamate after acute injections and a tolerance development in the neurotransmitters release and rats’ behavior after chronic treatment with 25I-NBOMe. The recreational use of 25I-NBOMe is associated with severe intoxication and deaths in humans. There is no data about 25I-NBOMe in vivo toxicity towards the brain tissue. In this article 25I-NBOMe-crossing through the blood–brain barrier (BBB), the impact on DNA damage, apoptosis induction, and changes in the number of cortical and hippocampal cells were studied. The presence of 25I-NBOMe in several brain regions shortly after the drug administration and its accumulation after multiple injections was found. The DNA damage was detected 72 h after the chronic treatment. On the contrary, at the same time point apoptotic signal was not identified. A decrease in the number of glial but not in neural cells in the frontal (FC) and medial prefrontal cortex (mPFC) was observed. The obtained data indicate that 25I-NBOMe passes easily across the BBB and accumulates in the brain tissue. Observed oxidative DNA damage may lead to the glial cells’ death.
Highlights
Experimental group Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg
In vitro activity of p21 (CDC42/RAC)-activated kinase 1 (PAK1) was reduced, and the QT interval measured by electrocardiography in rats was prolonged
The drug was detected in the rat blood plasma and brain regions 15 min after 1 and 10 mg/kg single doses of 25I-NBOMe (Table 1)
Summary
Experimental group Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg Control 1 mg/kg 10 mg/kg. In the in vitro studies, 25I-NBOMe decreased the viability of H9c2 cells and primary mice cardiomyocytes. In vitro studies with a close congener of this class, 25C-NBOMe (25–400 μM), showed a potent reduction of SN4741, SH-SY5Y, and PC12 cells viability indicating 50 times higher potency to reduce SH-SY5Y cells in respect to methamphetamine[15]. The incubation of the rat primary cortical cultures with 25B-NBOMe (30 μM) decreased neuronal activity that did not recover after 19 h of washout p eriod[16]. Our in vivo studies indicated that the low dose of 25B-NBOMe (0.3 mg/kg) was potent in damaging DNA in the rat frontal c ortex[17]. The present study aimed to assess the induction of in vivo neurotoxicity in the rat brain after single and repeated 25I-NBOMe treatment. An immunohistochemical assessment of cells number in the rat brain was studied
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