Selective Decrease in Serotonin Synthesis Rate in Rat Brainstem Raphe Nuclei Following Chronic Administration of Low Doses of Amitriptyline: an Effect Compatible with an Anti-Migraine Effect

The effects of chronic, low-dose amitriptyline on serotonin (5-HT) synthesis rate were measured in rat brain using autoradiography and the trapping of α-[14C]-methyl-L-tryptophan (α-[14C]-MTrp). Rats received amitriptyline (2 mg/kg per day) or saline via intraperitoneal osmotic minipumps for 21 days...

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Bibliographic Details
Published in:Cephalalgia 2003-06, Vol.23 (5), p.367-375
Main Authors: Pringsheim, T, Diksic, M, Dobson, C, Nguyen, K, Hamel, E
Format: Article
Language:English
Subjects:
5‐HT autoreceptors
Amitriptyline - administration & dosage
Analgesics, Non-Narcotic - administration & dosage
Animals
antidepressant
Brain Stem - drug effects
Brain Stem - metabolism
headache
Male
Migraine
Migraine Disorders - drug therapy
Migraine Disorders - metabolism
pain
Raphe Nuclei - drug effects
Raphe Nuclei - metabolism
Rats
Rats, Sprague-Dawley
Serotonin - biosynthesis
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Summary:The effects of chronic, low-dose amitriptyline on serotonin (5-HT) synthesis rate were measured in rat brain using autoradiography and the trapping of α-[14C]-methyl-L-tryptophan (α-[14C]-MTrp). Rats received amitriptyline (2 mg/kg per day) or saline via intraperitoneal osmotic minipumps for 21 days. Amitriptyline had no effect on any physiological parameters measured, or on free or total plasma tryptophan levels. However, amitriptyline exerted selective decreases of 15% and 17% (P < 0.001) in serotonin synthesis rates in the dorsal and median raphe nuclei, respectively. There was no reduction in any of the projection areas studied, including the cerebral cortex, hippocampus, thalamus, hypothalamus or striatum. The data suggest that chronic low doses of amitriptyline can lead to sustained 5-HT re-uptake inhibition selectively in the raphe nuclei, an effect compatible with tonic activation of 5-HT1A autoreceptors and inhibition of 5-HT synthesis. The failure of chronic amitriptyline treatment to affect 5-HT synthesis rate in the projection areas may ensure an adequate regulation of pain pathways implicated in migraine headache, an effect possibly related to amitriptyline anti-migraine efficacy.
ISSN:0333-1024
1468-2982
DOI:10.1046/j.1468-2982.2003.00526.x