Acute and chronic effects of citalopram on postsynaptic 5-hydroxytryptamine(1A) receptor-mediated feedback: a microdialysis study in the amygdala

• Published in: Journal of neurochemistry 2001-03, Vol.76 (6), p.1645-1653
• Main Authors: Bosker, F J, Cremers, T I, Jongsma, M E, Westerink, B H, Wikström, H V, den Boer, J A
• Format: Article
• Language: English
• Subjects: Amygdala - drug effects; Amygdala - physiology; Animals; Citalopram - administration & dosage; Citalopram - blood; Citalopram - pharmacology; Feedback - drug effects; Infusions, Parenteral; Kinetics; Male; Microdialysis; Piperazines - administration & dosage; Piperazines - pharmacology; Pyridines - administration & dosage; Pyridines - pharmacology; Rats; Rats, Wistar; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1; Serotonin - metabolism; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Synapses - drug effects; Synapses - physiology
• ISSN: 0022-3042
• DOI: 10.1046/j.1471-4159.2001.00194.x

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 microM) for 30 min into the amygdala maximally decreased 5-HT to 50% of basal level. Systemic administration of citalopram (10 micromol/kg) increased 5-HT to 175% of basal level. Local infusion of 1 microM 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 microM 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 micromol/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 microM 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.