Serotonergic lesioning differentially affects presynaptic and postsynaptic 5-HT_1B receptor mRNA levels in rat brain

The rat 5-HT_1B receptor (also referred to as the 5-HT_1Dβ receptor) is expressed in both serotonergic and nonserotonergic neurons in the rat brain, where it has been hypothesized to inhibit the release of neurotransmitters from axonal terminals. In this study we investigated the effect of chemical axotomy of serotonergic processes by 5,7-dihydroxytryptamine on the levels of 5-HT_1B mRNA in the dorsal raphe nucleus and several postsynaptic brain areas using in situ hybridization. 5,7-Dihydroxytryptamine (i.c.v.) reduced forebrain [³H]citalopram binding to serotonin transporter by 62-96% whereas binding in the dorsal raphe nucleus was preserved. Serotonin transporter mRNA hybridization signal in the dorsal raphe nucleus was only slightly reduced after 5,7-dihydroxytryptamine. These results suggest that our lesioning protocol caused axonal degeneration with preservation of most of the serotonergic perikarya in the dorsal raphe nucleus. 5-HT_1B mRNA hybridization signal in postsynaptic regions was unchanged by serotonergic lesions, but was markedly reduced in the dorsal raphe nucleus. Thus, disruption of serotonergic innervation affects the regulation of presynaptic and postsynaptic 5-HT_1B mRNA differently. Furthermore, although both 5-HT_1B receptors and serotonin transporters are found in serotonergic terminals, their levels may be regulated differentially during the period of regrowth that follows chemical axotomy.