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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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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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creator	Pringsheim, T Diksic, M Dobson, C Nguyen, K Hamel, E
description	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.
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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
title	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
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