Delta-9-tetrahydrocannabinol during pregnancy in the rat: effects on development of RNA, DNA, and protein in offspring brain.
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.
Morgan
B
B
New York State Psychiatric Institute, Department of Developmental Psychobiology, NY 10032.
Brake
S C
SC
Hutchings
D E
DE
Miller
N
N
Gamagaris
Z
Z
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000254:growth & development; D001923:Brain Chemistry / Q000187:drug effects*; D004247:DNA / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011506:Proteins / Q000032:analysis*; D012313:RNA / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D011506:Proteins; D012313:RNA; D013759:Dronabinol; D004247:DNA