title: A voltammetric and mathematical analysis of histaminergic modulation of serotonin in the mouse hypothalamus.
abstract: Histamine and serotonin are neuromodulators which facilitate numerous, diverse neurological functions. Being co-localized in many brain regions, these two neurotransmitters are thought to modulate one another's chemistry and are often implicated in the etiology of disease. Thus, it is desirable to interpret the in vivo chemistry underlying neurotransmission of these two molecules to better define their roles in health and disease. In this work, we describe a voltammetric approach to monitoring serotonin and histamine simultaneously in real time. Via electrical stimulation of the axonal bundles in the medial forebrain bundle, histamine release was evoked in the mouse premammillary nucleus. We found that histamine release was accompanied by a rapid, potent inhibition of serotonin in a concentration-dependent manner. We developed mathematical models to capture the experimental time courses of histamine and serotonin, which necessitated incorporation of an inhibitory receptor on serotonin neurons. We employed pharmacological experiments to verify that this serotonin inhibition was mediated by H3 receptors. Our novel approach provides fundamental mechanistic insights that can be used to examine the full extent of interconnectivity between histamine and serotonin in the brain. Histamine and serotonin are co-implicated in many of the brain's functions. In this paper, we develop a novel voltammetric method for simultaneous real-time monitoring of histamine and serotonin in the mouse premammillary nucleus. Electrical stimulation of the medial forebrain bundle evokes histamine and inhibits serotonin release. We show voltammetrically, mathematically, and pharmacologically that this serotonin inhibition is H3 receptor mediated.
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Srimal
authors.initials: S
authors.lastname: Samaranayake
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Abdalla
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Robke
authors.affiliation: Department of Biology, Duke University, Durham, North Carolina, USA.
authors.forename: H Frederik
authors.initials: HF
authors.lastname: Nijhout
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Reed
authors.affiliation: Department of Mathematics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Best
authors.affiliation: Department of Chemistry and Biochemistry, University of South Carolina, Columbia, South Carolina, USA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Hashemi
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D008474:Medial Forebrain Bundle / Q000378:metabolism; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018100:Receptors, Histamine H3; D012701:Serotonin; D006632:Histamine
keywords: H3 autoreceptor; carbon fiber microelectrodes; fast-scan cyclic voltammetry; heteroreceptor; thioperamide