Brain region‐specific alterations of 5‐HT2A and 5‐HT2C receptors in serotonin transporter knockout mice

The aim of the present studies was to determine the effects of reduced or absent serotonin (5‐HT) transporters (5‐HTTs) on 5‐HT2A and 5‐HT2C receptors. The density of 5‐HT2C receptors was significantly increased in the amygdala and choroid plexus of 5‐HTT knockout mice. On the other hand, the density of 5‐HT2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5‐HTT knockout mice. However, 5‐HT2A mRNA was not changed in any brain region measured. 5‐HT2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5‐HT2A receptors was evaluated by hormonal responses to (+/–)‐1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI). Oxytocin, but not adrenocorticotrophic hormone or corticosterone, responses to DOI were significantly greater in 5‐HTT knockout mice. In addition, Gq and G11 proteins were not significantly changed in any brain region measured. The present results suggest that the constitutive alteration in the function of 5‐HTTs changes the density of 5‐HT2A and 5‐HT2C receptors in a brain region‐specific manner. These changes may not be mediated by alterations in their gene expression or in the level of Gq/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5‐HTT knockout mice.