Expression level of 5‐HT1A receptor alters firing rate and concentration‐dependency in YFP‐labeled 5‐HT dorsal raphe neurons

Abstract

The serotonin (5‐HT) 1A receptor is implicated in the etiology of anxiety and depression. Depressed suicide victims show increased expression of the 5‐HT1A receptor, and transgenic 5‐HT1A receptor knockout (KO) mice have an anxiety phenotype. Both in vivo and in vitro electrophysiological recording techniques were used to assess the effects of 5‐HT1A receptor KO and overexpression (OE) on extracelullarly recorded firing rate and 5‐HT1A receptor mediated responses. There was no difference in firing rate between KO and wild‐type (WT) mice measured extracellularly in vivo or in brain slices in which YFP labeled 5‐HT neurons were activated with 10mM phenylephrine. 5‐HT1A receptor activation with 5‐CT inhibited firing in 5‐HT neurons in raphe brain slices from WT, but not KO, mice. 5‐HT neurons from OE mice showed decreased basal firing and a leftward shift of the 5‐HT1A concentration‐response (C‐R) curve compared to WT. The 5‐HT1A receptor antagonist WAY 100635 (100nM) had no effect on basal firing rate of OE or WT neurons, but blocked the inhibition by 5‐CT. Interestingly, whole cell recordings showed no difference in the C‐R curve for 5‐HT1A receptor‐mediated outward current. These results show that KO mice have no 5‐HT neuronal response to 5‐HT1A receptor activation, whereas OE mice have increased sensitivity compared to WT depending on the active state of the neuron. Supported by MH63078.