Acute and chronic effects of citalopram on postsynaptic 5‐hydroxytryptamine_1A 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¯esinoxan (0.3, 1, 3 mM) for 30 min into the amygdala maximally decreased 5-HT to 50% of basal level. Systemic administration of citalopram (10 mmol/kg) increased 5-HT to 175% of basal level. Local infusion of 1 mM 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 mM esinoxan for 30 min into the amygdala, which showed a signi®cant 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 mmol/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 mM WAY 100.635 into the amygdala now failed to augment the effect of citalopram. Both the¯esinoxan and WAY 100.635 data suggest an involvement of postsynaptic 5-HT 1A receptormediated feedback in the amygdala, which diminishes following chronic citalopram treatment. et al. 1994, 1996) and 5-HT synthesis (Hutson et al. 1989), while stimulation of 5-HT 1B presynaptic receptors decreases 5-HT release (Sharp et al. 1989;Limberger et al. 1991). These secondary phenomena are believed to limit the effect of re-uptake inhibition on the 5-HT release in the terminal regions.The delayed response to antidepressant treatment may be connected to a gradual loss of responsiveness of 5-HT autoreceptors following chronic treatment (Blier et al. 1987a). Theoretically, the latter condition can be mimicked

Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders

“…Although network changes might represent a central issue in antidepressant treatment (El Mansari et al, 2005), the driving factors are still far from understood. Previous studies in rats demonstrated 5-HT 1A receptor-mediated feedback loops from the medial prefrontal cortex (Casanovas et al, 1999;Sharp et al, 2007) and decreased responsiveness of amygdalar 5-HT 1A heteroreceptors after chronic SSRI treatment (Bosker et al, 2001). Together with desensitization of the raphe nuclei, these studies are consistent with our finding of enhanced 5-HT 1A correlations between amygdala and DRN after sustained escitalopram medication.…”

“…In healthy subjects, strong correlations of 5-HT 1A receptors between the dorsal raphe nucleus (DRN) and projection areas were reported (Rabiner et al, 2002;Borg et al, 2006;Drevets et al, 2007). Although these interregional relationships might provide important complementary information on a network level, only few results describe such treatment-induced interactions (Bosker et al, 2001;Sprouse et al, 2001;El Mansari et al, 2005).…”

‘It's the way that you look at it’—a cognitive neuropsychological account of SSRI action in depression

“…This is true both in preclinical studies measuring serotonin release with microdialysis [20] and in indirect measures in human volunteers employing, for example, the increase in salivary cortisol as an indirect index of enhanced serotonin activity [21]. In a task of emotional processing, we found that a single dose of the SSRI, citalopram (20 mg), increased the recognition of happy facial expressions [22].…”

Differential Regulation of 5-HT1A Receptor-G Protein Interactions in Brain Following Chronic Antidepressant Administration

“…Postsynaptic 5-HT 1A receptor-mediated feedback has been demonstrated in several terminal field areas of serotonergic innervation, including cortex (Ceci et al 1994;Casanovas et al 1999) and amygdala (Bosker et al 1997). Bosker et al (2001) Electrophysiological studies indicate that chronic treatment with amitriptyline results in the sensitization of postsynaptic neurons to serotonin in the hippocampus, where this response has been shown to be mediated by the 5-HT 1A receptor (de Montigny and Aghajanian 1978;Gallager and Bunney 1978;Chaput et al 1991). In the current study, however, we did not observe an increase in 5-HT 1A receptor-stimulated [ eas examined.…”