Postsynaptic 5-HT 1A receptors mediate 5-hydroxytryptamine release in the amygdala through a feedback to the caudal linear raphe

Abstract

Using brain microdialysis, it was demonstrated that the release of 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala is under inhibitory control of somatodendritic and postsynaptic 5-HT 1A receptors. Systemic administration of flesinoxan, a selective 5-HT 1A receptor agonist, significantly reduced the extracellular levels of 5-HT in the central nucleus of the amygdala. This effect could be completely antagonized by the 5-HT 1A receptor antagonist N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)- N-(2-pyridyl)cyclohexane carboxamine trihydrochloride (WAY 100635). Local administration of these compounds by reversed microdialysis into the raphe nuclei revealed that extracellular 5-HT levels in the central nucleus of the amygdala can be regulated through 5-HT 1A receptors in the caudal linear raphe nucleus, but not in the dorsal and median raphe nuclei. Interestingly, administration of flesinoxan into the central nucleus of the amygdala also decreased dialysate 5-HT levels both locally and in the caudal linear raphe nucleus. The former effect could be blocked by pretreatment with WAY 100635 when applied into the central nucleus of the amygdala, but not when applied into the caudal linear raphe nucleus. These data provide circumstantial evidence for the existence of a 5-HT 1A receptor mediated feedback loop from the central nucleus of the amygdala to the caudal linear raphe nucleus.