Prolactin response to dl-fenfluramine in panic disorder

doi:10.1016/0306-4530(93)90009-A

Psychoneuroendocrinology

Volume 18, Issues 5–6, 1993, Pages 337-342

https://doi.org/10.1016/0306-4530(93)90009-A Get rights and content

Abstract

The objective of this study was to test the hypothesis that serotonin receptors are hypersensitive in patients with panic disorder. Eleven patients and 12 controls received a single PO dose of 60 mg of dl-fenfluramine at 0900h on a single occasion. Blood samples were collected with an indwelling intravenous catheter at 30-min intervals from 0930h to 1530h and prolactin determined by radioimmunoassay. In both groups, fenfluramine induced a rise in the plasma prolactin concentration from baseline. The patients showed a greater increase in prolactin response than the normal controls. This result is consistent with the hypothesis of increased serotonin receptor function in patients with panic disorder.

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Citation Excerpt :
Several lines of evidence suggest that serotonergic dysregulation plays a role in the neurobiology of anxiety disorders. For example, panic disorder patients show significant differences in serotonergic activity compared with healthy control subjects, including 1) reduced 5-HT platelet transporter sites (Faludi et al 1994; McIntyre et al 1989; Norman et al 1990); 2) exaggerated neuroendocrine response to 5-HT agonists (Apostolopoulos et al 1993; Targum and Marshall 1989); and 3) heightened anxiety in response to some direct and indirect 5-HT agonists (Apostolopoulos et al 1993; George et al 1995; Kahn et al 1988; Klein et al 1991; Targum and Marshall 1989). Taken together, the sum of behavioral and neuroendocrine response studies with 5-HT agonists suggest the possibility of hypersensitive postsynaptic 5-HT receptors; however, this issue remains controversial because of a number of negative reported studies (Charney et al 1987; Germine et al 1994).
Although the cathecholamine systems have long been the focus of drug therapy in anxiety and depression, the development of novel drugs specifically aimed at new targets within these traditional neurotransmitter systems and at targets outside of these systems is now propelling the field of drug development in anxiety. A greater understanding of regional brain networks implicated in stress, anxiety, and anxious behaviors has provided localized targets for anxiolytics. Within the serotonin and norepinephrine systems, increased understanding of postsynaptic receptor regulation with chronic treatment and cross-system effects of drug therapy have been critical in furthering our understanding of effective pharmacological interventions. Receptors within the glutamate, γ-aminobutyric acid, and neuropeptide systems provide a rich diversity of drug targets, both in localization and function. While acknowledging significant clinical and biological differences between the various anxiety disorders, an important aspect of modern neurobiological research is to look for similarities among these disorders, given that they are highly comorbid with each other and often respond to the same spectrum of treatments. Here we review current views on both traditional and new molecular targets in the treatment of anxiety, realizing that the ultimate challenge in effective anxiolytic drug development may be achieving specificity in brain regions important in generating and sustaining anxiety.
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Serotonergic dysfunction has been postulated to play a role in the aetiology of social phobia. Buspirone, which is a partial agonist at 5HT1A receptors, increases prolactin release and may be used as a probe to examine serotonergic responses, dysfunction of which may be relevant to the pathophysiology of social phobia. We compared buspirone stimulated prolactin release in 14 patients with generalised social phobia and 14 healthy controls. Buspirone 30 mg was administered orally and prolactin release over 180 min was monitored. Overall, patients with generalised social phobia had greater prolactin release in response to buspirone challenge than healthy comparison subjects. There was no correlation between prolactin response and measures of severity of social phobia. Patients with generalised social phobia had enhanced central serotonergic responses, an abnormality shared with some other anxiety disorders and which may be of aetiological significance.
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Prolactin response to dl-fenfluramine in panic disorder

Abstract

Eur J Pharmacol

Biol Psychiatry

J Affect Dis

Biol Psychiatr

Psychiatr Res

Prog Neurobiol

Psychiatr Res

Serotonin function in anxiety II. Effects of the serotonin agonist mCPP in panic disorder patients and healthy controls

Psychopharmacology

Neuroendocrine responses to intravenous tryptophan in major depression

Arch Gen Psychiatry

Effect of a serotonin and noradrenalin uptake inhibitor in panic disorders: A double-blind comparative study with fluvoxamine and maprotiline

Int Clin Psychopharmacol