Brain region-specific alterations of 5-HT_2A and 5-HT_2C 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-HT_2A and 5-HT_2C receptors. The density of 5-HT_2C receptors was significantly increased in the amygdala and choroid plexus of 5-HTT knockout mice. On the other hand, the density of 5-HT_2A receptors was significantly increased in the hypothalamus and septum, but reduced in the striatum, of 5-HTT knockout mice. However, 5-HT_2A mRNA was not changed in any brain region measured. 5-HT_2C mRNA was significantly reduced in the choroid plexus and lateral habenula nucleus of these mice. The function of 5-HT_2A 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, G_q 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-HT_2A and 5-HT_2C receptors in a brain region-specific manner. These changes may not be mediated by alterations in their gene expression or in the level of G_q/11 proteins. The alterations in these receptors may be related to the altered behaviors of 5-HTT knockout mice.