The 5-HT1D/1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin

Abstract

This study measured the effects of the preferential 5-HT1D/1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test (SPST), which recruits the neural network involved in panic disorder and social anxiety disorder. In a double-blind, randomised experiment, 36 males received placebo (12), 50 mg (12) or 100 mg (12) of sumatriptan 2 h before the SPST. Subjective, physiological and hormonal measures were taken before, during and after the test. The dose of 100 mg of sumatriptan increased speech-induced fear more than either a 50mg dose of the drug or placebo. The largest dose of sumatriptan also enhanced vigilance more than placebo, without any change in blood pressure, heart rate or electrical skin conductance. Sumatriptan decreased plasma levels of prolactin. A significant but moderate increase in plasma cortisol after SPST occurred, independent of treatment. Because sumatriptan decreases 5-HT release into the extracellular space, the potentiation of SPST-induced fear caused by the drug supports the hypothesis that 5-HT attenuates this emotional state. As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin, in contrast to sumatriptan, the 5-HT regulation of stress-hormone release is likely to be different from that of emotion.

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

“…S4)-a time when eletriptan will still be present in the CNS 44 . This is to some extent expected, as 5-HT 1B/1D agonists increase social fear in rodents and humans 70,71 , but the effect is not observed in 16p11.2 DEL mice. Syntenic 16p11.2 deletion restricted to serotonergic neurones in mice reportedly decreases sociability-an effect that can be rescued by stimulation of 5-HT 1B receptors 24 .…”

Acute serotonergic treatment changes the relation between anxiety and HPA-axis functioning and periaqueductal gray activation

“…However, many studies have reported that treatment with acute SSRIs (fluoxetine, citalopram, sertraline, paroxetine) produced anxiety symptoms [6,38,39]. Two studies of particular interest have demonstrated that the administration of ESCIT or 5-HT 1D / 1B receptor agonist sumatriptan enhanced the level of fear response during a stressful simulated public speaking test, and this was accompanied by a remarkable increase of stress hormone [40,41]. Similarly, there is evidence from numerous animal behavioural studies also pointing to an anxiogenic response.…”

The 5-HT1B receptor - a potential target for antidepressant treatment

“…In humans, studies on the role of 5-HT 1B receptors in anxiety are disproportionately sparse. Increased fear of public speaking has been reported in healthy volunteers after administration of the 5-HT 1B/1D receptor agonist sumatriptan (de Rezende et al 2013 ). In the single in vivo brain imaging study of subjects with posttraumatic stress disorder, low 5-HT 1B receptor binding was described in the caudate, amygdala, and anterior cingulate cortex (ACC).…”