Exposure to methamidophos at adulthood elicits depressive-like behavior in mice.
Epidemiologic studies have suggested that organophosphate exposure is associated with an increased risk of depression and suicide. Considering that the neurobiological basis of this association is not well understood, in the present study we evaluated the depressive-like behavior of Swiss mice subchronically exposed to the organophosphate methamidophos at adulthood. From postnatal days 60 to 89 (PN60-PN89), one of two concentrations of methamidophos [higher dose (HiD): 5.25 microg/ml; lower dose (LoD): 1.31 microg/ml] or vehicle was administered in the drinking water. Immobile behavior, an animal model of depressive behavior, was assessed in the forced swimming and tail suspension tests either during (PN88) or after (PN99) the exposure period. On the subsequent day (PN89 or PN100), the Rota-rod and endurance swimming tests were used to evaluate motor performance. Brain acetylcholinesterase activity was quantified. During exposure, the LoD group presented increased immobility in the tail suspension test when compared to controls. The HiD group presented increased immobility in the forced swimming test when compared to LoD and control groups, an effect that emerged after cessation of exposure. There were no motor performance alterations. During exposure, acetylcholinesterase activity was inhibited in the HiD (43%) and LoD (15%) groups. After exposure, enzyme activity was reduced (25%) only in the HiD group. There were no signs of systemic toxicity. There were no correlations between acetylcholinesterase activity and behavioral measures. Our results indicate that methamidophos at doses below the threshold for systemic toxicity induces depressive-like behavior in adult mice.
Lima
Carla S
CS
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Av. Prof. Manoel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
Ribeiro-Carvalho
Anderson
A
Filgueiras
Cláudio C
CC
Manhães
Alex C
AC
Meyer
Armando
A
Abreu-Villaça
Yael
Y
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000139:chemically induced*; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D019417:Hindlimb Suspension; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D013550:Swimming
D007306:Insecticides; D009946:Organothiophosphorus Compounds; C014655:methamidophos; D000110:Acetylcholinesterase