Effect of chronic antidepressant treatment on 5-HT1B presynaptic heteroreceptors inhibiting acetylcholine release.

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.