25C-NBF, a new psychoactive substance, has addictive and neurotoxic potential in rodents

Arch Toxicol. 2020 Jul;94(7):2505-2516. doi: 10.1007/s00204-020-02740-3. Epub 2020 Apr 15.

Abstract

The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects. Considering that NPSs have caused unexpected harmful effects leading to emergency and even death, scientific confirmation of the potential adverse effects of 25C-NBF is essential. In the present study, we investigated whether 25C-NBF has addictive and neurotoxic potential and causes neurochemical changes. In addictive potential assessments, high conditioned place preference (CPP) scores and stable self-administration (SA) were observed in the 25C-NBF groups (CPP [3 mg kg-1]; SA [0.01, 0.03, 0.1 mg kg-1]), suggesting the addictive liability of 25C-NBF. In neurotoxic potential assessments, 25C-NBF treatment (single super-high dose [1 × 15, 30, 40 mg kg-1]; repeated high dose [4 × 8, 15, 30 mg kg-1]) resulted in reduced motor activity (open field test), abnormal motor coordination (rota-rod test) and impaired recognition memory (novel object recognition test), suggesting that 25C-NBF is neurotoxic leading to motor impairment and memory deficits. Subsequently, immunohistochemistry showed that 25C-NBF treatment decreased tyrosine hydroxylase (TH) expression and increased ionized calcium-binding adapter molecule 1 (Iba-1) expression in the striatum. Taken together, our results clearly demonstrate the dangers of recreational use of 25C-NBF, and we suggest that people stop using 25C-NBF and other NPSs whose pharmacological effects are not precisely known.

Keywords: 25C-NBF; Addiction; Neurochemical change; Neurotoxicity; New psychoactive substance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive / chemically induced*
  • Behavior, Addictive / metabolism
  • Behavior, Addictive / psychology
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Calcium-Binding Proteins / metabolism
  • Conditioning, Psychological / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Locomotion / drug effects
  • Male
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Microfilament Proteins / metabolism
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / physiopathology
  • Open Field Test / drug effects
  • Phenethylamines / toxicity*
  • Psychotropic Drugs / toxicity*
  • Rats, Sprague-Dawley
  • Rotarod Performance Test
  • Substance-Related Disorders / etiology*
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / psychology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Aif1 protein, mouse
  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Phenethylamines
  • Psychotropic Drugs
  • glial fibrillary astrocytic protein, mouse
  • Tyrosine 3-Monooxygenase