title: Organic cation transporter inhibition increases medial hypothalamic serotonin under basal conditions and during mild restraint.
abstract: The dorsomedial hypothalamus (DMH) has been implicated in the coordination of stress responses. Restraint stress or systemic corticosterone (CORT) treatment induces a rapid increase in tissue concentrations of serotonin (5-hydroxytryptamine; 5-HT) in the DMH. Although the mechanism for rapid changes in 5-HT concentrations in the DMH is not clear, earlier results suggest that stress-induced increases in CORT may inhibit 5-HT transport from the extracellular fluid by acting on corticosterone-sensitive organic cation transporters (OCTs). We tested the hypothesis that perfusion of the medial hypothalamus (MH), which includes the DMH, with the OCT blocker decynium 22 (D-22) would potentiate the effects of mild restraint on extracellular 5-HT. Male Sprague-Dawley rats, implanted with a microdialysis probe into the MH, were treated with reverse-dialysis of D-22 (20 microM; 40 min) or vehicle and subjected to either 40 min mild restraint or undisturbed control conditions. Perfusates collected from a separate group of rats were evaluated for the effect of restraint on extracellular CORT concentrations in the MH. Reverse-dialysis of D-22 induced an increase (200%) in extracellular 5-HT concentrations in the MH in undisturbed control rats. Restraint in the absence of D-22 did not significantly affect MH CORT or 5-HT concentrations. However, perfusion of the MH with D-22 during restraint led to an increased magnitude and duration of extracellular 5-HT concentrations, relative to D-22 by itself. These results are consistent with the hypothesis that OCTs in the DMH contribute to the clearance of 5-HT from the extracellular fluid under both baseline conditions and mild restraint.
authors.affiliation: Department of Biology, University of South Dakota, Vermillion, SD 57069-2390, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Lukkes
authors.forename: Miles
authors.initials: M
authors.lastname: Orchinik
authors.forename: Gina L
authors.initials: GL
authors.lastname: Forster
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Renner
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*
chemical_list: D027701:Organic Cation Transport Proteins; D011804:Quinolines; C100254:pseudoisocyanine; D012701:Serotonin; D003345:Corticosterone