PERINATAL DELTA(9)-TETRAHYDROCANNABINOL EXPOSURE DID NOT ALTER DOPAMINE TRANSPORTER AND TYROSINE-HYDROXYLASE MESSENGER-RNA LEVELS IN MIDBRAIN DOPAMINERGIC-NEURONS OF ADULT MALE AND FEMALE RATS

We have recently demonstrated that the magnitude of L-3,4-dihydroxyphe nylacetic acid (DOPAC) lowering effect caused by amphetamine in midbra in dopaminergic neurons of adult rats was lesser in animals that had b een perinatally exposed to Delta(9)-tetrahydrocannabinol (Delta(9)-THC ) than controls. In the present study, we have examined whether this l oss in the responsiveness to amphetamine might be due to changes at th e level of dopamine transporter (DAT), the main molecular site for the action of amphetamine, following the perinatal exposure to Delta(9)-T HC. To this end, we have analyzed DAT mRNA levels, by using in situ hy bridization, in the substantia nigra and ventral tegmental al ea, the areas where cell bodies of DAT-containing midbrain neurons are located , of adult male and female rats that had been perinatally exposed to D elta(9)-THC. In addition, we also analyzed mRNA levels of tyrosine hyd roxylase (TH), the rate-limiting enzyme in DA synthesis. Results were as follows. Both adult male and fe male rats that had been perinatally exposed to Delta(9)-THC exhibited similar mRNA levels to controls for both DAT and TH in the substantia nigra as well as in the ventral teg mental area. This observation makes it difficult to support the idea t hat the differences found in adulthood after pharmacological challenge s were caused by irreversible changes at the level of gene expression for these two key proteins. (C) 1998 Elsevier Science Inc.