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

Microdialysis was used to assess the involvement of postsynaptic 5‐hydroxytryptamine1A (5‐HT1A) receptors in the regulation of extracellular 5‐HT in the amygdala. Local infusion of the 5‐HT1A 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‐HT1A receptor antagonist WAY 100.635 into the amygdala augmented the effect of citalopram to more than 500% of basal 5‐HT level. 5‐HT1A 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‐HT1A receptor‐mediated feedback in the amygdala, which diminishes following chronic citalopram treatment.