Estrogenic modulation of delta(9)-Tetrahydrocannabinol effects on nigrostriatal dopaminergic activity in the female rat brain
Abstract
In this work we studied the possible estrogenic modulation of the effects of delta(9)-tetrahydrocannabinol (THC) on nigrostriatal dopaminergic activity. Thus, we examined the effects of an acute dose of this cannabinoid: (i) during the three phases of the estrous cycle; (ii) after ovariectomy, chronic estrogen replacement, and/or tamoxifen (TMX)-induced blockade of cytosolic estrogenic receptors; and (iii) combined with a single and physiological injection of estradiol to ovariectomized rats, whose effects were measured early, with no time for genomic induction. THC increased the activity of tyrosine hydroxylase in the striatum of ovariectomized rats implanted with estradiol-filled Silastic capsules or ovariectomized rats. This effect: (i) depended on the presence of an intact estrogenic receptor mechanism, because it was prevented by pretreatment with TMX, and (ii) did not appear when THC was coadministered with estradiol, suggesting an inhibitory modulation of cannabinoid effect by the nongenomic mechanism of action of this steroid. The striatal content of l-3,4-dihydroxyphenylacetic acid and its ratio with dopamine content, which can be used as an index of neuronal activity, also increased following acute THC administration....Continue Reading
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