Effects of buspirone on plasma neurotransmitters in healthy subjects

Abstract

Buspirone is an anxiolytic drug which exerts several central effects. It antagonizes presynaptic inhibitory DA2 autoreceptors at dopaminergic neurons and acts as an agonist for 5-HT1A inhibitor autoreceptors at serotonergic cells. Thus, buspirone respectively enhances and depresses the firing rates of both type of neurons. At doses which correlate with dopaminergic stimulation, but not 5-HT inhibition, buspirone also increases the firing rates of the central noradrenergic cells. We measured levels of circulating neurotransmitters before and up to 240 minutes after the oral administration of 20 mg of buspirone in 32 healthy volunteers. Buspirone significantly increased levels of noradrenaline, dopamine, and free serotonin but did not affect levels of adrenaline, 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 noradrenaline and dopamine levels. The strength and significance of these correlations were increased by using the noradrenaline/adrenaline ratio instead of noradrenaline absolute values. This finding indicates that increases in both noradrenaline and dopamine arise from sympathetic nerves rather than the adrenal glands. We also found significant negative correlations between free serotonin increases and systolic blood pressure-heart rate decreases. Our results indicate that buspirone stimulates 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 addition, buspirone increases free serotonin plasma concentrations and decreases systolic blood pressure plus heart rate levels through mechanisms associated with parasympathetic activation.

Central Nervous System Circuitry Involved in the Hyperinsulinism Syndrome

“…With respect to this, it should be remembered that anxiety is positively correlated with DR-5HT but not MR-5HT activity [88]. These findings fit well with others showing that 5HT 1A agonists, like buspirone, suppress anxiety and inhibit the DR-5HT but not MR-5HT neurons which are mainly provided with 5HT 1B inhibitory receptors [89]. …”

Estrogen Prevents 5-HT1A Receptor-Induced Disruptions of Prepulse Inhibition in Healthy Women

“…While buspirone is known as a partial 5-HT 1A receptor agonist, at higher doses it has some antagonist activity at dopamine D 2 -like receptors and indirect agonist activity at adrenergic receptors (Lechin et al, 1998). However, the disruptive effect of buspirone treatment on PPI in humans was similar to that of 8-OH-DPAT treatment in rats (Gogos and Van den Buuse, 2004), while administration of dopamine D 2 -like receptor antagonists increased PPI in rats (Johansson et al, 1995).…”

Role of the Serotonergic System in Reduced Pulmonary Function after Exposure to Methamphetamine

“…It was subsequently shown that tianeptine, an SSRE that reduces free 5-HT through enhancing uptake, provokes a rapid and significant decrease of both clinical rating and free 5-HT plasma levels associated with improved pulmonary function (6,22). Conversely, buspirone, which increases free 5-HT in plasma, triggered asthma attacks in patients with asthma (23). The recent finding that intravenous administration of MA to rats results in a transient, significant increase in plasma 5-HT prompted us to explore whether the increased AR observed in mice after inhalation exposure to low-dose MA could be related to perturbation of the serotonergic system in the lung.…”