Type II pyrethroid deltamethrin produces antidepressant-like effects in mice.
Pyrethroids, which are widely used insecticides with low acute toxicity in mammals, affect sodium channels in neurons. In primary culture of rat cortical neurons, the type II pyrethroid deltamethrin (DM) markedly enhances the expression of the mRNA of brain-derived neurotrophic factor (BDNF) and exerts neurotrophic effects. In this study, we investigated the antidepressant-like effect of DM in mice. The effects of DM were assessed using the forced swimming test (FST) and were compared with those of type I pyrethroid permethrin (PM). Intraperitoneal administration of DM (5 and 10mg/kg), but not of PM (10mg/kg), increased the expression of BDNF mRNA in the hippocampus. DM, but not PM, significantly decreased the immobility time in the FST, and did not affect locomotor activity and motor coordination, suggesting that DM has an antidepressant-like effect. This effect of DM was inhibited by intracerebroventricular injection of K252a, which is an inhibitor of the BDNF receptor TrkB, indicating that the antidepressant-like effects of DM are mediated by BDNF/TrkB signaling pathways. Repeated administration of DM, but not of PM, also exerted antidepressant-like effects, which were long lasting. The results of the present study suggest that DM possesses antidepressant-like properties, and may be a possible source for the development of drugs to treat neurodegenerative and psychiatric disorders including depression.
Department of Pharmacology, Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan; Molecular Genetic Research, Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: takasaki@eng.u-toyama.ac.jp.
Ichiro
I
Takasaki
Kyohei
K
Oose
Yuki
Y
Otaki
Daisuke
D
Ihara
Mamoru
M
Fukuchi
Akiko
A
Tabuchi
Hiroshi
H
Tsuneki
Yoshiaki
Y
Tabuchi
Takashi
T
Kondo
Akiyoshi
A
Saitoh
Mitsuhiko
M
Yamada
Masaaki
M
Tsuda
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002227:Carbazoles / Q000008:administration & dosage; D003863:Depression / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D026121:Indole Alkaloids / Q000008:administration & dosage; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011722:Pyrethrins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; C049985:staurosporine aglycone
Antidepressant; BDNF; DM; Deltamethrin; FST; Forced swimming test; Hippocampus; PM; Permethrin; brain-derived neurotrophic factor; deltamethrin; forced swimming test; permethrin