Chronic treatment with citalopram facilitates the effect of a challenge dose on cortical serotonin output: role of presynaptic 5-HT1A receptors.
In animals given citalopram (10 mg/kg) twice daily for 14 days a further dose of 1 mg/kg, administered 24 h after the last dose, markedly increased cortical dialysate serotonin (5-hydroxytryptamine, 5-HT), but had no effect in control animals. The effect on dialysate 5-HT in the dorsal raphe was not increased by the chronic treatment. At 25 micrograms/kg, 8-hydroxy-2-(di-n-propylamino)tetralin, an agonist at 5-HT1A receptors, reduced cortical 5-HT output in controls but not in animals treated chronically with citalopram whereas 50 micrograms/kg reduced 5-HT output in both groups. These findings suggest that somatodendritic 5-HT1A receptors are desensitized after chronic treatment with citalopram and this results in facilitation of its effect on cortical dialysate 5-HT. These results also agree with the concept that the effect of 5-HT re-uptake inhibitors on increasing 5-HT output in the frontal cortex is attenuated by their simultaneous ability to activate somatodendritic 5-HT1A receptors via an increase of endogenous 5-HT in the raphe region.
Invernizzi
R
R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Bramante
M
M
Samanin
R
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D003956:Dialysis; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015283:Citalopram; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors