title: Serotonin releasers increase prepulse inhibition in serotonin 1B knockout mice.
abstract: BACKGROUND
  Prepulse inhibition (PPI) is the normal reduction of the startle response which occurs when an abrupt startling stimulus is preceded by a weak pre-stimulus and is decreased in several neuropsychiatric disorders.
  
  
  OBJECTIVE
  The role of the serotonin 1B (5-HT(1B)) receptor in modulating PPI was investigated using 5-HT-releasing agents in wild-type (WT) and 5-HT1B knockout (1BKO) mice. Whether the differential effects of 5-HT-releasing agents on PPI in WT and 1BKO mice resulted from lack of the 5-HT1B receptor or altered development was also assessed.
  
  
  METHODS
  PPI was assessed in WT and 1BKO mice treated with the 5-HT-releasing agents (+)3,4-methylenedioxy-N-methylamphetamine (MDMA: 0, 10 mg/kg) or (+/-)N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB: 0, 10 mg/kg). Additionally, intact 129 Sv mice received pre-treatments of the 5-HT1B/1D antagonist GR 127935 (0, 0.75, 1.5, 3.0 mg/kg) and treatments of MDMA (10 mg/kg).
  
  
  RESULTS
  MDMA and MBDB increased PPI in 1BKO mice, but did not alter PPI in WT mice. Intact 129 Sv mice receiving 3.0 mg/kg GR 127935 and 10 mg/kg MDMA exhibited increases in PPI.
  
  
  CONCLUSIONS
  The ability of GR 127935 to increase PPI in intact MDMA-treated mice suggests that lack of the 5-HT1B receptor, and not altered development, is responsible for the PPI-increasing effects of 5-HT releasers in 1BKO mice. 5-HT release activates multiple 5-HT receptor subtypes, which individually may increase or decrease PPI and together have a combined effect on PPI. Our finding that MDMA and MBDB increase PPI in 1BKO, but not WT mice, indicates that the activation of 5-HT1B receptors by 5-HT disrupts PPI.
authors.affiliation: Department of Neuroscience, University of California at San Diego, La Jolla, 92093-0804, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Dulawa
authors.forename: K A
authors.initials: KA
authors.lastname: Scearce-Levie
authors.forename: R
authors.initials: R
authors.lastname: Hen
authors.forename: M A
authors.initials: MA
authors.lastname: Geyer
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D010069:Oxadiazoles; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; C051570:N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine; C090701:GR 127935; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine