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Effect of chronic antidepressant treatment on 5-HT1B presynaptic heteroreceptors inhibiting acetylcholine release
F Bolaños-Jiménez1, R Manhães de Castro, G Fillion
1Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
Abstract:
The effect of long term treatment with two tricyclic antidepressants on the sensitivity of 5-HT1B presynaptic heteroreceptors inhibiting acetylcholine (ACh) release was investigated. Groups of male rats received during 14 days either saline, citalopram (20 mg/kg), a serotonin (5-HT) uptake blocker, or tianeptine (2 x 10 mg/kg), an antidepressant that enhances 5-HT uptake. The efficacy of the 5-HT1B selective agonist 7-trifluoromethyl-4-(4-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (CGS 12066B) in reducing K(+)-evoked [3H]acetylcholine release from hippocampal synaptosomes was determined 24 hr after the last administration. The chronic treatment with citalopram or tianeptine modified neither the basal nor the K(+)-evoked release of [3H]acetylcholine. In contrast, these treatments significantly reduced the efficacy of CGS 12066B to inhibit the release of [3H]acetylcholine induced by K+ depolarization. These data suggest that chronic antidepressant treatment desensitizes 5-HT1B presynaptic heteroreceptors through a mechanism which seems to be independent of the synaptic availability of 5-HT.
Insights
Long-term antidepressant treatment with citalopram or tianeptine desensitizes serotonin 5-HT1B presynaptic heteroreceptors. This desensitization reduces the receptors' ability to inhibit acetylcholine release, independent of serotonin levels.
Area of Science:
- Neuropharmacology
- Neuroscience
- Biochemistry
Background:
- Serotonin 5-HT1B receptors are presynaptic heteroreceptors that regulate neurotransmitter release, including acetylcholine (ACh).
- Tricyclic antidepressants (TCAs) like citalopram and tianeptine are widely used for treating depression and can modulate serotonergic pathways.
Purpose of the Study:
- To investigate the long-term effects of citalopram and tianeptine on the sensitivity of 5-HT1B presynaptic heteroreceptors.
- To determine if chronic antidepressant treatment alters the inhibitory effect of 5-HT1B receptor activation on acetylcholine release.
Main Methods:
- Male rats were treated for 14 days with saline, citalopram, or tianeptine.
- The efficacy of a 5-HT1B selective agonist (CGS 12066B) in reducing K(+)-evoked [3H]acetylcholine release from hippocampal synaptosomes was assessed 24 hours after the final drug administration.
Main Results:
- Chronic citalopram or tianeptine treatment did not alter basal or K(+)-evoked [3H]acetylcholine release.
- Both antidepressant treatments significantly reduced the inhibitory efficacy of the 5-HT1B agonist CGS 12066B on K(+)-evoked [3H]acetylcholine release.
Conclusions:
- Chronic treatment with citalopram and tianeptine leads to desensitization of 5-HT1B presynaptic heteroreceptors.
- This desensitization appears to be independent of changes in synaptic serotonin availability.