Distribution of indoleamines and [3H]paroxetine binding in rat brain regions following acute or perinatal delta 9-tetrahydrocannabinol treatments.
The effects of delta 9-tetrahydrocannabinol (delta 9-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 marker of 5-HT uptake sites. Two different delta 9-THC 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 delta 9-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 delta 9-THC produced different effects on the central 5-HT system of the offspring, with a clear regional specificity, but with no changes in the densities of 5-HT uptake sites.
Molina-Holgado
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Departamento de Biología Animal II, Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Spain.
Molina-Holgado
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Leret
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ML
González
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Reader
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TA
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D007032:Hypothalamus, Anterior / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000378:metabolism; D017374:Paroxetine / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D012701:Serotonin; D017374:Paroxetine; D006897:Hydroxyindoleacetic Acid; D013759:Dronabinol