The Amygdala Regulates the Pituitary-Adrenocortical Response and Release of Hypothalamic Serotonin following Electrical Stimulation of the Dorsal Raphe Nucleus in the Rat

Abstract

The amygdala is known to modulate the function of the hypothalamo-pituitary-adrenocortical (HPA) axis, but the mechanism of this effect is still not clear. In the present study we examined the specific role of the serotonin (5-HT) system in mediating the effect of the amygdala on the activity of the HPA axis. Bilateral lesions of the amygdala in rats reduced the adrenocorticotropin (ACTH) and corticosterone responses to electrical stimulation of the dorsal raphe nucleus, where the cell bodies of serotonergic neurons are located. Amygdala lesions had no effect on the ACTH and corticosterone responses to administration of a 5-HT_1A receptor agonist directly into the paraventricular nucleus (PVN) of the hypothalamus, indicating that there was no impairment in the activity of postsynaptic 5-HT_1A receptors in the hypothalamus. In vivo microdialysis showed that amygdala lesions markedly attenuated the effect of electrical stimulation of the dorsal raphe to increase extracellular secretion of 5-HT in the PVN. This is the first demonstration that the amygdala has a facilitatory effect on the function of dorsal raphe 5-HT neurons which project to the PVN, and suggests a mechanism by which the amygdala may modulate the function of the HPA axis.

The Role of the Amygdala in Regulating the Hypothalamic-Pituitary-Adrenal Axis

“…We have previously demonstrated that the activation of central AMG has a facilitatory efect on the function of the dorsal raphe nucleus 5-HT neurons, which project to the PVN, suggesting a mechanism by which this structure may modulate the HPA axis responses [31]. In particular, we examined the role of the central AMG in modulating the HPA axis responses to speciic hypothalamic noradrenergic and glutamate stimulation.…”

“…It has been demonstrated that these projections include neurons containing CRH that in this case function as a neurotransmiter in the AMG. These neurons activate, noradrenergic and serotonergic output from brainstem nuclei [26,28,30,31]. These nuclei play an essential role in the activation of the HPA axis upon exposure to stressful stimuli, including immune challenges [32].…”

“…To explore a possible mechanism by which the AMG afects the HPA axis function, we examined the speciic role of the serotonergic system in mediating the efect of the AMG on the activity of the HPA axis [31]. Bilateral lesions of the AMG in rats reduced ACTH and CS responses to electrical stimulation of the dorsal raphe nucleus, where the cell bodies of serotonergic neurons are located.…”

Vulnerability to depression: what is the role of stress genes in gene × environment interaction?

“…It is well established that the activity of the amygdala is associated with the HPA axis through serotonergic projections to the hypothalamus (Weidenfeld et al 2002), influencing the stress response (Herman et al 2005). It has also been suggested that the central amygdaloid nucleus takes part in overproduction of CRF in melancholic patients with hypercortisolaemia (Reul & Holsboer, 2002).…”

Effects of Early Life Stress on [11C]DASB Positron Emission Tomography Imaging of Serotonin Transporters in Adolescent Peer- and Mother-Reared Rhesus Monkeys

“…During the early postnatal period, 5-HT plays a pivotal role in the development of the CNS (Buznikov et al, 2001), and 5-HT neurotransmission is involved in both activation and feedback control of the neuroendocrine stress axis (Weidenfeld et al, 2002). In turn, stress hormones are also involved in regulating the expression of certain serotonin system genes, including that for the serotonin transporter (SERT) (Tafet et al, 2001).…”