Prolactin response to fenfluramine in abstinent, alcohol-dependent patients.
ABSTRACT It has been suggested that serotonin (5HT) function is abnormal in alcoholics even during abstinence. The prolactin response to fenfluramine (PRF) is generally believed to reflect the activity of the 5HT system and has been previously used to investigate 5HT activity in a variety of conditions, including alcoholism. The origin of the cortisol (CORT) response to fenfluramine is less clear. The objectives of this paper are to examine the prolactin (PRL) and CORT response to dl-fenfluramine in a large cohort of males with alcohol dependence who had been abstinent for 3 weeks, and to compare this with an age-matched control group. Ninety-four subjects with a DSM-III-R diagnosis of moderate to severe alcohol dependence who had been abstinent for 3 weeks, and 23 control subjects underwent neuroendocrine challenge with dl-fenfluramine (10 mg per 10 kg body weight). PRL and CORT responses were measured. No significant difference was found in PRF between abstinent, alcoholic patients and controls (F = 2.7, d.f. = 1.115, P = 0.10). CORT response was significantly lower in abstinent alcoholics than in controls (F = 10.0, d.f. = 1.116, P = 0.002). The results suggest no clear difference in 5HT function between abstinent alcoholics and healthy controls. The reduced CORT response in abstinent alcoholics further supports evidence of hypofunction of the adrenocortical system in this group.
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ABSTRACT: The plasma prolactin response to a single-dose fenfluramine challenge is increasingly utilized in psychiatric research as an indirect and noninvasive measure of central serotonergic activity. However, the influences of age, gender, and body weight on prolactin response and characterization of physical and psychological symptoms evoked by fenfluramine remain poorly studied. In the current study, 83 nonpatient male and female volunteers, 25-60 years old, were administered a standardized fenfluramine challenge test (60 mg). Serial blood samples for plasma drug concentration and plasma prolactin concentration were obtained and side effects reported by participants were recorded. Analyses revealed that both plasma drug concentration and prolactin response were correlated with weight-relative dose (r = 0.43 and r = 0.38, respectively; p < 0.001). No significant relationship was noted between prolactin response and either age or gender. Symptoms during fenfluramine challenge were reported by 90% of subjects, most commonly fatigue, headache, lightheadedness, and difficulty concentrating. Overall side effect severity was related to weight-relative dose (r = 0.26; p < 0.05) and prolactin response (r = 0.42; p < 0.001). We conclude that fenfluramine challenge results should be reported as change in plasma prolactin relative to dose, and that in nonpatient samples the test is associated with frequent side effects.Biological Psychiatry 05/1996; 39(9):761-8. · 9.25 Impact Factor
- Molecular Aspects of Medicine 02/1992; 13(3):205-20. · 10.38 Impact Factor
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ABSTRACT: The role of vasopressin (AVP) as a stress hormone in man is still a matter of controversy. Thus, the response of plasma AVP, among other hormones, to either intravenously injected human corticotropin releasing factor (hCRF, in the absence or presence of the opioid antagonist naloxone) or a combined 5-minute stress test was compared in healthy men (n = 10) and short-term abstinent alcoholics (n = 11), a group with recognized abnormalities of humoral stress parameters. Stimuli were applied blindly and in random order, one per day, in a 3-day experimental block. A second block using the same standardized protocol was carried out 12 weeks later. Alcoholics entered block I 8 days after the last ethanol ingestion. Up to block II, they were strictly controlled for abstinence. On each experimental day, subjects remained supine from 0700h until 1500h. Stimuli were applied alternatively at 1030h each day. Fourteen blood samples were drawn per day with simultaneous fluid substitution. There were no significant changes in plasma AVP as an acute response to any of the stimuli in either group or block. However, unexpectedly, controls had significantly higher basal AVP levels throughout block I as compared with block II without concomitant changes in plasma osmolality or blood pressure. Further analysis of the data revealed that the dramatically increased AVP levels of the five younger control subjects for this difference. In fact, AVP levels in the five older healthy subjects and in all alcoholics remained low throughout the two blocks. Our data suggest that plasma AVP is continuously elevated in healthy young men upon anticipation of novelty. In contrast, healthy men of the older are group and early abstinent alcoholics seem to lack such a sustained AVP response.Psychoneuroendocrinology 02/1997; · 5.14 Impact Factor