Learning deficits expressed as delayed extinction of a conditioned running response following perinatal exposure to vinclozolin.
Vinclozolin (Vz) is one member of a group of fungicides whose metabolites are androgen receptor antagonists. These fungicides have been shown to block androgen-driven development and compromise reproductive function. The current study sought to determine if Vz also affects learning following exposure to low doses during the perinatal period. To test this, an androgen-dependent behavior was examined, the extinction of a previously reinforced running response. Pregnant Long-Evans rats were administered a daily oral dose of 0, 1.5, 3, 6 or 12 mg/kg Vz from the 14th day of gestation through postnatal day 3. After reaching adulthood, male and female offspring were trained to run through a short alleyway for food reinforcement. Acquisition of the response was not affected by Vz exposure. However, males required more trials than females for response extinction once food was no longer available in the apparatus. Males exposed to 6 or 12 mg/kg Vz failed to show any extinction by the end of the procedure, while the lowest dose of Vz appeared to facilitate extinction in both male and female offspring. These results demonstrate that endocrine disrupting antiandrogens can alter nervous system development in addition to the reproductive system.
André
Susan M
SM
Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104, United States.
Markowski
Vincent P
VP
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects*; D005260:Female; D005262:Feminization / Q000139:chemically induced; D005659:Fungicides, Industrial / Q000633:toxicity*; D007859:Learning Disabilities / Q000139:chemically induced* / Q000523:psychology*; D008297:Male; D010080:Oxazoles / Q000633:toxicity*; D010413:Penis / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012018:Reflex / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects; D012420:Running / Q000523:psychology*; D012727:Sex Characteristics
D000726:Androgen Antagonists; D005659:Fungicides, Industrial; D010080:Oxazoles; C025643:vinclozolin