Snyder-Keller A, Sam C, Keller R W
Wadsworth Center, New York State Department of Health, P.O. Box 509, Albany, NY 12201, USA.
Neurotoxicol Teratol. 2000 Mar-Apr;22(2):231-6. doi: 10.1016/s0892-0362(99)00061-6.
We previously reported that prenatal cocaine exposure increased susceptibility to cocaine-induced seizures later in life. Here we examine whether this enhanced susceptibility to seizures generalizes to other chemoconvulsants, and whether postnatal cocaine treatment similarly increases susceptibility. Following prenatal cocaine treatment (40 mg/kg; E10-20), both male and female rats were more likely to seize to a dose of 30 mg/kg pentylenetetrazol (PTZ) at 2 months of age, although the severity of the seizures observed was increased only in females. Daily cocaine injections (10-20 mg/kg SC) during the first 10 days after birth also produced effects that were dependent on the sex of the animal. Postnatally cocaine-treated female rats showed no greater incidence of seizures in response to an acute high dose of cocaine, but did exhibit an increased susceptibility to cocaine-kindled seizures. Male, but not female, postnatally cocaine-treated rats were more susceptible to PTZ-induced seizures. The increased susceptibility to seizures induced by two different chemoconvulsants after prenatal cocaine treatment suggests that developmental cocaine exposure, particularly during the second trimester equivalent, alters the balance between excitation and inhibition in the brain.
我们之前报道过,产前接触可卡因会增加日后生活中对可卡因诱发癫痫发作的易感性。在此,我们研究这种对癫痫发作增强的易感性是否会推广到其他化学惊厥剂,以及产后给予可卡因是否同样会增加易感性。在产前给予可卡因治疗(40毫克/千克;胚胎期第10至20天)后,雄性和雌性大鼠在2月龄时对30毫克/千克戊四氮(PTZ)的剂量更易出现惊厥发作,尽管观察到的惊厥严重程度仅在雌性大鼠中有所增加。出生后前10天每日注射可卡因(10至20毫克/千克,皮下注射)也产生了取决于动物性别的效应。产后接受可卡因治疗的雌性大鼠对急性高剂量可卡因的惊厥发作发生率没有更高,但对可卡因点燃的惊厥确实表现出易感性增加。产后接受可卡因治疗的雄性大鼠(而非雌性大鼠)对PTZ诱发的惊厥更易感。产前可卡因治疗后对两种不同化学惊厥剂诱发惊厥的易感性增加表明,发育过程中接触可卡因,尤其是在相当于人类孕期第二个三月期时,会改变大脑中兴奋与抑制之间的平衡。