Figure 2.

Graphic representation of 5HT projections from the raphe nuclei (RN). The dorsal RN (DRN) sends stimulatory projections to the central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST), which participate in increased fear and anxiety, inhibitory projections to the periaqueductal grey (PAG) and the striatum, which participate in passive behavior, inhibitory projections to the medial prefrontal cortex (MPFC), and stimulatory projections to the nucleus accumbens (NAc), which participate in the regulation of complex behaviors and expression of emotions. Conversely, the MPFC sends inhibitory projections to the DRN and the amygdala, which may be translated into anti-anxiety effect. The medial RN (MRN) sends stimulatory projections to the hippocampus, which have been associated to increased tolerance to adverse stimuli and decreased anxiety. Under repeated uncontrollable stress the amygdala is increasingly stimulated by the DRN, which results in increased anxiety, the PAG and striatum are inhibited by the DRN, with the resulting passivity, and the serotonergic activation from the MRN to the hippocampus results impaired. Increased reactivity of the amygdala and decreased activation of the hippocampus may lead to increased activation of the hypothalamic-pituitary-adrenal (HPA) axis. Successful treatment is translated into recovery of these feedback mechanisms, with the consequent normalization of cortisol, decreased amygdala reactivity, increased hippocampal function, and normalization of the serotonergic systems.