Cloperastine rescues impairment of passive avoidance response in mice prenatally exposed to diethylstilbestrol.
We previously reported that prenatal exposure to diethylstilbestrol (DES) impaired passive avoidance responses in mice. Apart from the above, we also found that cloperastine, a centrally acting antitussive, ameliorated depression-like and anxiety-like behaviors in rodents at antitussive-effective doses. In this study, we investigated whether or not cloperastine rescues impairment of passive avoidance responses in mice prenatally exposed to DES. Male DES-exposed mice were subcutaneously administered cloperastine at 10 or 30 mg/kg twice a day from 32 to 41 days after birth and subjected to behavioral testing 42 to 46 days after birth. Cloperastine at 10 and 30 mg/kg ameliorated DES-induced impairment of passive avoidance responses. In addition, cloperastine affected the levels of 5-HT1A receptors, GIRK and BDNF in the hippocampus of DES-exposed mice. However, the number of BrdU-positive cells in the hippocampus of DES-exposed mice was not changed by chronic administration of cloperastine. These findings suggest that the action of endocrine disruptors in the brain may not always be irreversible, and that the symptoms caused by endocrine disruptors might be curable with drugs such as cloperastine.
Department of Environmental and Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Fumio
F
Soeda
Emi
E
Hirakawa
Masako
M
Inoue
Tetsuya
T
Shirasaki
Kazuo
K
Takahama
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001362:Avoidance Learning / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004054:Diethylstilbestrol / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism
D000996:Antitussive Agents; D019208:Brain-Derived Neurotrophic Factor; D052244:Endocrine Disruptors; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497069:Kcnj6 protein, mouse; D018696:Neuroprotective Agents; D010880:Piperidines; D044282:Receptor, Serotonin, 5-HT1A; C040282:cloperastine; D004054:Diethylstilbestrol