title: Activation of 5-HT1A receptors in the preBötzinger region has little impact on the respiratory pattern.
abstract: The preBötzinger (preBötC) complex has been suggested as the primary site where systemically administered selective serotonin agonists have been shown to reduce or prevent opioid-induced depression of breathing. However, this hypothesis has not been tested pharmacologically in vivo. This study sought to determine whether 5-HT1A receptors within the preBötC and ventral respiratory column (VRC) mediate the tachypneic response induced by intravenous (IV) (±)-8-Hydroxy-2-diproplyaminotetralin hydrobromide (8-OH-DPAT) in a decerebrated dog model. IV 8-OH-DPAT (19 ± 2 μg/kg) reduced both inspiratory (I) and expiratory (E) durations by ∼ 40%, but had no effect on peak phrenic activity (PPA). Picoejection of 1, 10, and 100 μM 8-OH-DPAT on I and E preBötC neurons produced dose-dependent decreases up to ∼ 40% in peak discharge. Surprisingly, microinjections of 8-OH-DPAT and 5-HT within the VRC from the obex to 9 mm rostral had no effect on timing and PPA. These results suggest that the tachypneic effects of IV 8-OH-DPAT are due to receptors located outside of the areas we studied.
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, United States.
authors: Tomislav
authors: T
authors: Radocaj
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, United States.
authors: Sanda
authors: S
authors: Mustapic
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, United States.
authors: Ivana
authors: I
authors: Prkic
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Children's Hospital of Wisconsin, Pediatric Anesthesia, Milwaukee, WI, United States.
authors: Astrid G
authors: AG
authors: Stucke
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, United States.
authors: Francis A
authors: FA
authors: Hopp
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Children's Hospital of Wisconsin, Pediatric Anesthesia, Milwaukee, WI, United States.
authors: Eckehard A E
authors: EA
authors: Stuth
authors: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States; Clement J. Zablocki VA Medical Center, Milwaukee, WI 53295, United States. Electronic address: ezuperku@mcw.edu.
authors: Edward J
authors: EJ
authors: Zuperku
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000633:toxicity; D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000633:toxicity; D059246:Tachypnea / Q000139:chemically induced / Q000473:pathology*
chemical_list: D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin
keywords: 5-HT receptors; 5-HT(1A) receptors; 8-OH-DPAT; Control of breathing; Respiratory neurons; preBötzinger complex