Yasuhara F, Kempinas W G, Pereira O C M
Department of Pharmacology, Institute of Biosciences, Sao Paulo State University UNESP, 18618-000 Botucatu, Sao Paulo, Brazil.
Reprod Toxicol. 2005 Mar-Apr;19(4):541-6. doi: 10.1016/j.reprotox.2004.08.006.
Previous studies in rats suggested that picrotoxin, a GABA(A) receptor antagonist, may cause long-term changes in male reproductive physiology and behavior in rats exposed during prenatal and postnatal periods. The present study has further examined this phenomenon. Wistar rat dams were dosed subcutaneously with 0.75 mg/kg picrotoxin in saline, or vehicle alone, during the perinatal period (day 19 of gestation, immediately after parturition, and once a day during the first 5 days of lactation). Birth weight and sexual maturation of pups were unchanged; however, plasma testosterone levels and sexual behavior was altered in male offspring. Although fertile, these males showed altered mating behavior in terms of a decrease in the mean number of mounts during a 30-min observation period with normal females. Some showed homosexual behavior when castrated and pretreated with exogenous estrogen. These findings suggest that perinatal exposure to picrotoxin alters sexual dimorphism in the developing rat brain, manifesting as altered reproductive performance and sexual behavior of males.
先前对大鼠的研究表明，印防己毒素作为一种γ-氨基丁酸A型（GABA(A)）受体拮抗剂，可能会使在产前和产后接触该物质的大鼠的雄性生殖生理和行为发生长期变化。本研究进一步探究了这一现象。在围产期（妊娠第19天、分娩后即刻以及哺乳期的前5天每天一次），给Wistar大鼠母鼠皮下注射0.75毫克/千克溶于生理盐水的印防己毒素，或仅注射赋形剂。幼崽的出生体重和性成熟未受影响；然而，雄性后代的血浆睾酮水平和性行为发生了改变。尽管这些雄性具有生育能力，但在与正常雌性进行30分钟观察期的交配行为中，其平均爬跨次数减少。一些大鼠在阉割并接受外源性雌激素预处理后表现出同性恋行为。这些发现表明，围产期接触印防己毒素会改变发育中大鼠大脑的性二态性，表现为雄性生殖性能和性行为的改变。
