No 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

It is unlikely that the difference in 5-HT(1A) properties between LAL and SAL mice is an adaptive compensatory reaction to changes in 5-HT metabolism. Although unspecific motor effects, at least in SAL mice, cannot be ruled out, it is suggested that the behavioral effects of 8-OH-DPAT and S-15535 may be mediated by predominant activation of postsynaptic 5-HT(1A) receptors in LAL mice and by presynaptic 5-HT(1A) receptors in SAL mice.