title: 2-Phenylethylamine, a constituent of chocolate and wine, causes mitochondrial complex-I inhibition, generation of hydroxyl radicals and depletion of striatal biogenic amines leading to psycho-motor dysfunctions in Balb/c mice.
abstract: Behavioral and neurochemical effects of chronic administration of high doses of 2-phenylethylamine (PEA; 25-75 mg/kg, i.p. for up to 7 days) have been investigated in Balb/c mice. Depression and anxiety, as demonstrated respectively by increased floating time in forced swim test, and reduction in number of entries and the time spent in the open arms in an elevated plus maze were observed in these animals. General motor disabilities in terms of akinesia, catalepsy and decreased swimming ability were also observed in these animals. Acute and sub-acute administration of PEA caused significant, dose-dependent depletion of striatal dopamine, and its metabolites levels. PEA caused dose-dependent generation of hydroxyl radicals in vitro in Fenton's reaction in test tubes, in isolated mitochondrial fraction, and in vivo in the striatum of mice. A significant inhibition of NADH-ubiquinone oxidoreductase (complex-I; EC: 1.6.5.3) activity suggests the inhibition in oxidative phosphorylation in the mitochondria resulting in hydroxyl radical generation. Nissl staining and TH immnunohistochemistry in brain sections failed to show any morphological aberrations in dopaminergic neurons or nerve terminals. Long-term over-consumption of PEA containing food items could be a neurological risk factor having significant pathological relevance to disease conditions such as depression or motor dysfunction. However, per-oral administration of higher doses of PEA (75-125 mg/kg; 7 days) failed to cause such overt neurochemical effects in rats, which suggested safe consumption of food items rich in this trace amine by normal population.
authors.affiliation: Laboratory of Clinical and Experimental Neurosciences, Division of Cell Biology and Physiology, Indian Institute of Chemical Biology (CSIR, Govt. of India), 4 Raja S C Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: T
authors.initials: T
authors.lastname: Sengupta
authors.forename: K P
authors.initials: KP
authors.lastname: Mohanakumar
mesh_terms: D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D002099:Cacao / Q000737:chemistry*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D010627:Phenethylamines / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects*; D014920:Wine / Q000032:analysis*
chemical_list: D001679:Biogenic Amines; D010627:Phenethylamines; C029261:phenethylamine; D017665:Hydroxyl Radical; D042967:Electron Transport Complex I