PMID- 8968950
OWN - NLM
STAT- MEDLINE
DCOM- 19970407
LR  - 20181113
IS  - 0895-8696 (Print)
IS  - 0895-8696 (Linking)
VI  - 7
IP  - 4
DP  - 1996 Winter
TI  - Effects of perinatal exposure to delta 9-tetrahydrocannabinol on the fetal and 
      early postnatal development of tyrosine hydroxylase-containing neurons in rat 
      brain.
PG  - 291-308
AB  - The exposure of pregnant rats to delta 9-tetrahydrocannabinol (delta 9-THC), the 
      main psychoactive constituent of Cannabis sativa, during the perinatal period 
      affects the gene expression and the activity of tyrosine hydroxylase (TH) in the 
      brains of their offspring at peripubertal and adult ages. In the present work we 
      explored whether these effects also appear during fetal and early neonatal 
      periods, when TH expression plays an important role in neural development. To 
      this end, the mRNA amounts for TH and the amounts and activity of this enzyme, in 
      addition to catecholamine (CA) contents, were analyzed in the brain of fetuses at 
      different gestational days (GD) and of newborns at two postnatal ages, which had 
      been daily exposed to delta 9-THC or vehicle from d 5 of gestation. Results were 
      as follows. The exposure to delta 9-THC markedly affected the expression of the 
      TH gene in the brain of fetuses at GD 14. Thus, the amounts of its mRNA at this 
      age were higher in delta 9-THC-exposed fetuses than in controls. This 
      corresponded with a marked rise in the amounts of TH protein and in the activity 
      of this enzyme at this age. Normalization was found in these parameters at GD16. 
      However, a marked sexual dimorphism in the response of TH gene to cannabinoid 
      exposure appeared from GD18 and was particularly evident at GD21, when TH-mRNA 
      amounts increased in developing female brains, but decreased in developing male 
      brains exposed to delta 9-THC, effects that were mostly prolonged to early 
      postnatal ages. However, these changes did not correspond always with parallel 
      changes in the amounts and activity of TH and in CA contents, as occurred in 
      GD14, suggesting that delta 9-THC would not be affecting the basal capability to 
      synthesize CAs in TH-containing neurons, but would affect the responsiveness of 
      TH gene. We found only a marked increase in the production of 
      L-3,4-dihydroxyphenylacetic acid, the main intraneuronal dopamine metabolite, in 
      female newborns exposed to delta 9-THC. Collectively, our results support the 
      belief that the perinatal exposure to delta 9-THC affects the expression of the 
      TH gene and, sometimes, the activity of this enzyme in brain catecholaminergic 
      neurons in certain critical periods of fetal and early neonatal brain 
      development. These results support the notion that cannabinoids are able to 
      affect the gene expression of specific key proteins for catecholaminergic 
      development, and that these alterations might be the origin of important 
      long-term neurobehavioral effects caused by perinatal cannabinoid exposure at 
      peripubertal and adult ages.
FAU - Bonnin, A
AU  - Bonnin A
AD  - Instituto Complutense de Drogodependencias, Department of Biochemistry, Faculty 
      of Medicine, Complutense University, Madrid, Spain.
FAU - de Miguel, R
AU  - de Miguel R
FAU - Castro, J G
AU  - Castro JG
FAU - Ramos, J A
AU  - Ramos JA
FAU - Fernandez-Ruiz, J J
AU  - Fernandez-Ruiz JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 102-32-9 (3,4-Dihydroxyphenylacetic Acid)
RN  - 7J8897W37S (Dronabinol)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - 3,4-Dihydroxyphenylacetic Acid/metabolism
MH  - Aging
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/embryology/*enzymology/growth & development
MH  - Dronabinol/*pharmacology
MH  - Female
MH  - Gene Expression Regulation, Developmental/*drug effects
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Gestational Age
MH  - Male
MH  - Neurons/*enzymology/physiology
MH  - Norepinephrine/metabolism
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Wistar
MH  - Sex Characteristics
MH  - Tyrosine 3-Monooxygenase/*biosynthesis
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 10.1007/BF02737066 [doi]
PST - ppublish
SO  - J Mol Neurosci. 1996 Winter;7(4):291-308. doi: 10.1007/BF02737066.