EFFECTS OF BUSPIRONE ON PLASMA NEUROTRANSMITTERS IN HEALTHY-SUBJECTS

Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA(2) autoreceptors at dopaminer gic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depre sses the firing rates of both type of neurons. At doses which correlat e with dopaminergic stimulation, but not 5-HT inhibition, buspirone al so increases the firing rates of the central noradrenergic cells. We m easured levels of circulating neurotransmitters before and up to 240 m inutes after the oral administration of 20 mg of buspirone in 32 healt hy volunteers. Buspirone significantly increased levels of noradrenali ne, dopamine, and free serotonin but did not affect levels of adrenali ne, tryptophane, or platelet serotonin. Small but significant drops in systolic blood pressure and heart rate were observed after buspirone ingestion. Atropine administration before buspirone ingestion annulled the free serotonin increase as well as systolic blood pressure-heart rate decrease. We found significant positive correlations between nora drenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline rati o instead of noradrenaline absolute values. This finding indicates tha t increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negat ive correlations between free serotonin increases and systolic blood p ressure-heart rate decreases. Our results indicate that buspirone stim ulates central sympathetic activity. These acute effects of buspirone are reflected in an increased peripheral neural sympathetic activity, but not adrenal sympathetic activity in healthy individuals. In additi on, buspirone increases free serotonin plasma concentrations and decre ases systolic blood pressure plus heart rate levels through mechanisms associated with parasympathetic activation.