Johns Josephine M, Lubin Deborah A, Lieberman Jeffrey A, Lauder Jean M
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7096, USA.
Dev Neurosci. 2002;24(6):522-30. doi: 10.1159/000069363.
Prenatal cocaine exposure results in behavioral abnormalities throughout development in rats, but little is known regarding the biological mechanisms underlying these abnormalities. Pregnant rats received subcutaneous twice-daily injections (1 ml/kg) of normal saline or 15 mg/kg of cocaine hydrochloride throughout gestation (gestation days 1-20). Following delivery, pups were placed with untreated surrogates. Male and female pups were killed on postnatal days 30, 60 or 120 for assessment of 5-HT(1A) receptor development in the forebrain, diencephalon, midbrain and pons using radiolabel immunocytochemistry. Findings revealed gender and age differences in developmental regulation of 5-HT(1A) receptors, indicating that male rats are more susceptible to long-term consequences of prenatal cocaine exposure in comparison to females. This study also demonstrates gender-specific development of serotonin (5-HT(1A)) receptors across postnatal ages, demonstrating a fundamentally different pattern of development of 5-HT(1A) receptors between males and females.
孕期接触可卡因会导致大鼠在整个发育过程中出现行为异常,但对于这些异常背后的生物学机制却知之甚少。怀孕大鼠在整个妊娠期(妊娠第1至20天)每天接受两次皮下注射(1毫升/千克)生理盐水或15毫克/千克盐酸可卡因。分娩后,幼崽由未处理的代孕母鼠抚养。在出生后第30、60或120天处死雄性和雌性幼崽,使用放射性标记免疫细胞化学方法评估前脑、间脑、中脑和脑桥中5-HT(1A)受体的发育情况。研究结果揭示了5-HT(1A)受体发育调节中的性别和年龄差异,表明与雌性相比,雄性大鼠更容易受到产前接触可卡因的长期影响。这项研究还证明了出生后不同年龄段血清素(5-HT(1A))受体的性别特异性发育,表明雄性和雌性之间5-HT(1A)受体的发育模式存在根本差异。