Effects of perinatal exposure to delta-9-tetrahydrocannabinol on the emotional reactivity of the offspring: a longitudinal behavioral study in Wistar rats
The effects of Δ9-tetrahydrocannabinol (Δ9-tetrahydrocannabinol-THC) 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 [3H]paroxetine as a maker of 5-HT uptake sites. Two different Δ9-THC treatments were chosen, i.e: acute and chronic perinatal maternal exposure. Following acute treatment (5mg/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 Δ9-THC (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 [3H]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 Δ9-THC 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.