Acute and chronic effects of citalopram on postsynaptic 5-hydroxytryptamine1A receptor-mediated feedback: a microdialysis study in the amygdala

ABSTRACT

Microdialysis was used to assess the involvement of postsynaptic 5-hydroxytryptamine_1A (5-HT_1A) receptors in the regulation of extracellular 5-HT in the amygdala. Local infusion of the 5-HT_1A receptor agonist flesinoxan (0.3, 1, 3 µm) for 30 min into the amygdala maximally decreased 5-HT to 50% of basal level. Systemic administration of citalopram (10 µmol/kg) increased 5-HT to 175% of basal level. Local infusion of 1 µm of the 5-HT_1A receptor antagonist WAY 100.635 into the amygdala augmented the effect of citalopram to more than 500% of basal 5-HT level. 5-HT_1A receptor responsiveness after chronic citalopram treatment was determined in two ways. First, by local infusion of 1 µm flesinoxan for 30 min into the amygdala, which showed a significant 63% reduction in response (area under the concentration–time curve; AUC) for the citalopram group compared to the saline group. Second, by systemic administration of citalopram (10 µmol/kg), which increased 5-HT to 350% of basal level. The effect was larger than in untreated animals, but more important, local infusion of 1 µm WAY 100.635 into the amygdala now failed to augment the effect of citalopram. Both the flesinoxan and WAY 100.635 data suggest an involvement of postsynaptic 5-HT_1A receptor-mediated feedback in the amygdala, which diminishes following chronic citalopram treatment.