Pharmacological challenge with a serotonin 1D agonist in alcohol dependence.
BACKGROUND
Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink.


METHODS
Fifteen patients with alcohol dependence who had undergone detoxification were recruited. Sumatriptan (100 mg) and placebo was administered in cross-over fashion on 2 separate days 72 hours apart. Both patients and raters were blind to all treatments. Patients were assessed on the following scales at -30, 0, 30, 90, 150 and 210 minutes: A 6-item scale designed to rate the patient's intention to drink; The Sensation Scale; a 13-item affect analog scale designed to rate the pattern and extent of emotional changes; and an 8-item scale designed to rate the patient's craving for alcohol.


RESULTS
No significant differences were found between the placebo and sumatriptan groups and no significant cross over effects were found.


CONCLUSIONS
The general lack of efficacy of sumatriptan in producing alcohol-like symptoms or a desire to drink alcohol may suggest that the 5HT1D receptor plays little role in the pathophysiology of alcoholism.
Vythilingum
Bavanisha
B
MRC, Dept of Psychiatry, University of Stellenbosch, South Africa. bv@sun.ac.za
Hugo
Charmaine J
CJ
Maritz
J Stefan
JS
Pienaar
Willie
W
Stein
Dan J
DJ
D000428:Alcohol Drinking / Q000503:physiopathology / Q000523:psychology; D000437:Alcoholism / Q000503:physiopathology* / Q000523:psychology; D016739:Behavior, Addictive / Q000503:physiopathology / Q000523:psychology; D018592:Cross-Over Studies; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010555:Personality Inventory; D010919:Placebos; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D011795:Surveys and Questionnaires; D009435:Synaptic Transmission / Q000502:physiology
D010919:Placebos; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018170:Sumatriptan