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Distribution of indoleamines and [3H]paroxetine binding in rat brain regions following acute or perinatal Δ9-tetrahydrocannabinol treatments

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Abstract

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.

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Abbreviations

Hypo:

anterior hypothalamus

Cin:

cingulate cortex

dHipp:

dorsal hippocampus

5-HIAA:

5-hydroxyindole-3-acetic acid

HPLC:

high-performance liquid chromatography

5-HT:

serotonin

5-HTP:

5 hydroxy-1-tryptophan

LC:

Locus coeruleus

rNS:

rostral neostriatum

MRN:

midbrain Raphe nuclei region

SN:

Substantia nigra

Δ9-THC:

Δ9-Tetrahydrocannabinol

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Authors and Affiliations

  1. Departamento de Biología Animal II, Fisiología Animal, Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Madrid, Spain

    Francisco Molina-Holgado, María L. Leret & María I. González

  2. Centre de recherche en sciences neurologiques, Département de physiologie, Faculté de Médecine, Université de Montréal, Succursale A, C.P. 6128, H3C 3J7, Montréal, Québec, Canada

    Eduardo Molina-Holgado &  Tomás A. Reader

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Molina-Holgado, F., Molina-Holgado, E., Leret, M.L. et al. Distribution of indoleamines and [3H]paroxetine binding in rat brain regions following acute or perinatal Δ9-tetrahydrocannabinol treatments. Neurochem Res 18, 1183–1191 (1993). https://doi.org/10.1007/BF00978372

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