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.
Bolaños-Jiménez
F
F
Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
Manhães de Castro
R
R
Fillion
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D011810:Quinoxalines; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D013841:Thiazepines; D015283:Citalopram; C050504:tianeptine; C052561:CGS 12066B; D000109:Acetylcholine; D011188:Potassium