Perinatal delta9-tetrahydrocannabinol exposure did not alter dopamine transporter and tyrosine hydroxylase mRNA levels in midbrain dopaminergic neurons of adult male and female rats.
We have recently demonstrated that the magnitude of L-3,4-dihydroxyphenylacetic acid (DOPAC) lowering effect caused by amphetamine in midbrain dopaminergic neurons of adult rats was lesser in animals that had been perinatally exposed to delta9-tetrahydrocannabinol (delta9-THC) than controls. In the present study, we have examined whether this loss in the responsiveness to amphetamine might be due to changes at the level of dopamine transporter (DAT), the main molecular site for the action of amphetamine, following the perinatal exposure to delta9-THC. To this end, we have analyzed DAT mRNA levels, by using in situ hybridization, in the substantia nigra and ventral tegmental area, the areas where cell bodies of DAT-containing midbrain neurons are located, of adult male and female rats that had been perinatally exposed to delta9-THC. In addition, we also analyzed mRNA levels of tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis. Results were as follows. Both adult male and female rats that had been perinatally exposed to delta9-THC exhibited similar mRNA levels to controls for both DAT and TH in the substantia nigra as well as in the ventral tegmental area. This observation makes it difficult to support the idea that the differences found in adulthood after pharmacological challenges were caused by irreversible changes at the level of gene expression for these two key proteins.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
L
L
García-Gil
J A
JA
Ramos
T
T
Rubino
D
D
Parolaro
J J
JJ
Fernández-Ruiz
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011619:Psychotropic Drugs; D012333:RNA, Messenger; C493216:Slc6a3 protein, rat; D013759:Dronabinol; D014446:Tyrosine 3-Monooxygenase