Buspirone modulates basal and fluoxetine-stimulated dialysate levels of dopamine, noradrenaline and serotonin in the frontal cortex of freely moving rats: activation of serotonin1A receptors and blockade of α2-adrenergic receptors underlie its actions

Autor: Mark Millan, Jean-Michel Rivet, C. Melon, Alain Gobert, Laetitia Cistarelli
Rok vydání: 1999
Předmět:
Male
Agonist
Serotonin
medicine.medical_specialty
Pyridines
medicine.drug_class
Dopamine
Microdialysis
Serotonin reuptake inhibitor
Pharmacology
Piperazines
Buspirone
Norepinephrine
chemistry.chemical_compound
Dopamine receptor D3
Fluoxetine
Dopamine receptor D2
Internal medicine
medicine
Animals
Drug Interactions
Rats
Wistar
Neurotransmitter
Oxazoles
Adrenergic alpha-Antagonists
Chromatography
High Pressure Liquid
Brain Chemistry
Raclopride
8-Hydroxy-2-(di-n-propylamino)tetralin
General Neuroscience
Neural Inhibition
Adrenergic alpha-2 Receptor Antagonists
Frontal Lobe
Rats
Serotonin Receptor Agonists
Endocrinology
chemistry
Receptors
Serotonin
Dopamine Antagonists
Serotonin Antagonists
Adrenergic alpha-Agonists
Receptors
Serotonin
5-HT1
Locomotion
Selective Serotonin Reuptake Inhibitors
Endogenous agonist
medicine.drug
Zdroj: Neuroscience. 93:1251-1262
ISSN: 0306-4522
DOI: 10.1016/s0306-4522(99)00211-0
Popis: The serotonin1A receptor partial agonist, buspirone, also displays antagonist properties at D2 receptors and is metabolized to the alpha2-adrenergic receptor antagonist, 1-(2-pyrimidinyl-piperazine). Herein, we examined mechanisms underlying the influence of buspirone alone, and in association with the serotonin reuptake inhibitor, fluoxetine, upon extracellular levels of serotonin, dopamine and noradrenaline simultaneously quantified in the frontal cortex of freely moving rats. Buspirone (0.01-2.5 mg/kg, s.c.) dose-dependently decreased dialysate levels of serotonin (-50%), and increased those of dopamine (+100%) and noradrenaline (+140%). The reduction by buspirone of serotonin levels was abolished by the serotonin1A receptor antagonist, WAY 100,635 (0.16), which did not, however, modify its influence upon dopamine and noradrenaline. In contrast to buspirone, the serotonin reuptake inhibitor, fluoxetine (10.0), increased frontocortical levels of serotonin (+ 120%), dopamine (+55%) and noradrenaline (+90%). Buspirone dose-dependently (0.01-2.5) decreased the induction by fluoxetine of serotonin levels yet potentiated (three-fold) its elevation of dopamine and noradrenaline levels. The serotonin1A agonist, 8-hydroxy-2-(di-n-propyl-amino)-tetralin (0.16), mimicked the action of buspirone in reducing resting levels of serotonin (-60%) and in enhancing those of dopamine (+135%) and noradrenaline (+165%). Like buspirone, it attenuated the influence of fluoxetine upon serotonin levels, yet facilitated its influence upon dopamine and noradrenaline levels. In contrast, WAY 100,635 selectively potentiated the increase in levels of serotonin (two-fold) versus dopamine and noradrenaline elicited by fluoxetine. Further, WAY 100,635 abolished the inhibitory influence of buspirone upon fluoxetine-induced serotonin release, but only partly interfered with its potentiation of fluoxetine-induced increases in dopamine and noradrenaline levels. The D2/D3 receptor antagonist, raclopride (0.16), increased basal dopamine (+60%) levels but little influenced those of serotonin and noradrenaline, and failed to modify the action of fluoxetine. The alpha2-adrenergic receptor antagonist, 1-(2-pyrimidinyl-piperazine) (2.5), which did not modify resting levels of serotonin, markedly increased those of dopamine (+90%) and noradrenaline (+190%) and potentiated (two-fold) the increases in dialysate levels of dopamine, noradrenaline and serotonin provoked by fluoxetine. Further, the alpha2-adrenergic receptor agonist, S18616, attenuated the enhancement by buspirone of the fluoxetine-induced increase in levels of dopamine and noradrenaline. In conclusion, the inhibitory influence of buspirone upon resting and fluoxetine-stimulated serotonin levels reflects its agonist properties at serotonin1A autoreceptors. The facilitatory influence of buspirone upon resting and fluoxetine-stimulated dopamine and noradrenaline levels may also involve its serotonin1A properties. However, its principal mechanism of action in this respect is probably the alpha2-adrenergic antagonist properties of its metabolite, 1-(2-pyrimidinyl-piperazine). The present observations are of significance to experimental and clinical studies of the influence of buspirone upon depressive states, alone and in association with antidepressant agents.
Databáze: OpenAIRE
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