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 μg/kg, 8-hydroxy-2-(di-n-propylamino) tetralin, an agonist at 5-HT_1A receptors, reduced cortical 5-HT output in controls but not in animals treated chronically with citalopram whereas 50 μg/kg reduced 5-HT output in both groups. These findings suggest that somatodendritic 5-HT_1A receptors are desentisized 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-HT_1A receptors via an increase of endogenous 5-HT in the raphe region.