DISTRIBUTION OF INDOLEAMINES AND [H-3] PAROXETINE BINDING IN RAT-BRAIN REGIONS FOLLOWING ACUTE OR PERINATAL DELTA(9)-TETRAHYDROCANNABINOL TREATMENTS

The effects of DELTA9-tetrahydrocannabinol (DELTA9-THE) administration on the central serotoninergic system were evaluated by biochemical assays of tissue levels of indoleamines; a measure of the serotonin (5-HT) innervation was obtained by using [H-3]paroxetine as a marker of 5-HT uptake sites. Two different DELTA9-THE treatments were chosen, i.e.: acute and chronic perinatal maternal exposure. Following acute treatment (5 mg/kg), the 5-HT content increased in dorsal hippocampus (+35%), Substantia nigra (+61%) and neostriatum (+62%) but remained unchanged in cingulate cortex, Raphe nuclei, Locus coeruleus and anterior hypothalamus. Endogenous 5-hydroxyindole-3-acetic acid (5-HIAA) decreased in anterior hypothalamus (-23%) and Raphe nuclei (-21%). Following maternal exposure to DELTA9-THE (5 mg/kg per day; from gestational day 13 to postnatal day 7), levels of 5-HT were increased in the neostriatum (+22%) but decreased in anterior hypothalamus (-25%), Raphe nuclei (-29%) and Locus coeruleus (-20%)of the litters. Tissue 5-HIAA was increased in anterior hypothalamus (+23%) and Substantia nigra (+48%). There were no changes in 5-HT uptake site density, determined by [H-3]paroxetine binding, except for an increase (+50%) in the cingulate cortex of perinatal-treated rats when compared to acutely-treated animals. The present results show that acute and maternal exposure to DELTA9-THE produced different effects on the central 5-HT system of the offspring, with a clear regional especifity, but with no changes in the densities of 5-HT uptake sites.