Figure 7.

Schematic drawing illustrating the putative interactions between the serotonergic and histaminergic systems. Histamine (HA) neurons are localized exclusively in the tuberomamillary nucleus (TMN) of the posterior hypothalamus. The TMN receives dense serotonergic projections from the raphe nuclei (Ericson et al., 1989), and 5-HT depolarizes HA neurons by activating 5-HT_2C receptors (Eriksson et al., 2001). In turn, activation of HA H₁ receptor (H₁R) on dorsal raphe neurons increases the serotonergic neuron firing rate (Bárbara et al., 2002; Brown et al., 2002). The disruption of this loop in HA-deprived mice supposedly prevents CREB phosphorylation in the hippocampus and is responsible for the inefficacy of selective serotonin reuptake inhibitors (SSRIs) in the tail suspension test (TST). Blockade of 5-HT_2c receptors in the TMN inhibits HA release in the cortex. H_nR, histamine receptors.