Morgan B, Brake S C, Hutchings D E, Miller N, Gamagaris Z
New York State Psychiatric Institute, Department of Developmental Psychobiology, NY 10032.
Pharmacol Biochem Behav. 1988 Oct;31(2):365-9. doi: 10.1016/0091-3057(88)90359-0.
Either 15 or 50 mg/kg of delta-9-tetrahydrocannabinol (THC) was administered from Day 2 through Day 22 of gestation. Pair-fed and nontreated groups served as controls and all treated and control litters were fostered at birth to untreated dams. To determine the effects of THC on offspring brain development, DNA, RNA and protein values were determined at 7, 14, and 21 days of postnatal age. DNA and RNA levels appeared unaffected by THC but brain protein levels of the 50 mg/kg offspring were significantly lower than in the other groups at Day 7 and 14. This suggests that the high THC dose inhibited protein synthesis for at least the first 14 days of life. Subsequently, protein levels of the 50 mg/kg offspring increased rapidly so that there were no differences between any of the groups at 21 days of age. These findings for developing CNS parallel the delayed rate of somatic growth previously reported from our laboratory and suggest a transitory rather than a permanent effect of THC on both somatic and brain growth. We also found that THC produces a significant dose-related increase in the sex-ratio of live male-to-female offspring, a finding we have reported previously.
在妊娠第2天至第22天期间,给予15或50毫克/千克的Δ⁹-四氢大麻酚(THC)。配对喂养组和未处理组作为对照,所有处理组和对照组的幼崽在出生时寄养给未处理的母鼠。为了确定THC对后代大脑发育的影响,在出生后7天、14天和21天测定DNA、RNA和蛋白质值。DNA和RNA水平似乎不受THC影响,但在出生后第7天和第14天,50毫克/千克组后代的脑蛋白水平显著低于其他组。这表明高剂量的THC至少在出生后的前14天抑制了蛋白质合成。随后,50毫克/千克组后代的蛋白质水平迅速上升,因此在21日龄时,各组之间没有差异。这些关于中枢神经系统发育的发现与我们实验室先前报道的躯体生长延迟率一致,表明THC对躯体和大脑生长的影响是暂时的而非永久性的。我们还发现,THC会使存活的雄性与雌性后代的性别比显著增加,这一发现我们之前已经报道过。