title: Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice.
abstract: BACKGROUND
  Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce.
  
  
  OBJECTIVE
  To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects.
  
  
  METHODS
  Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field and formalin tests.
  
  
  RESULTS
  2064H was shown to bind to the serotonin 2C (5-HT2C) receptor, a known target for depression and pain treatment. 2064H showed 59.6% inhibition of binding of [3H]-mesulergine with an IC50value of 179 ng/mL and did not show inhibition of binding greater than 45% with any other receptors tested. Both 2064H and 2064H3 decreased immobility time in the first minute of the tail suspension test. 2064H increased time, distance and number of entries in the center region in the first half of the open field test. 2064H increased overall nocifensive behaviors in the formalin test.
  
  
  CONCLUSIONS
  Overall, manipulating the 5-HT2Creceptor with these receptor-specific ligands derived from cyanobacteria altered pain, depression and anxiety-like behaviors, illustrating the importance of this receptor in affective behaviors. These results demonstrate the potential of cyanobacteria as a source for CNS active compounds.
authors.affiliation: a Department of Biological Sciences , Duquesne University , Pittsburgh , PA , USA.|b Duquesne University Chronic Pain Research Consortium , Pittsburgh , PA , USA.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Lax
authors.affiliation: b Duquesne University Chronic Pain Research Consortium , Pittsburgh , PA , USA.|c Duquesne University Mylan School of Pharmacy , Pittsburgh , PA , USA.
authors.forename: Kh Tanvir
authors.initials: KT
authors.lastname: Ahmed
authors.affiliation: a Department of Biological Sciences , Duquesne University , Pittsburgh , PA , USA.|b Duquesne University Chronic Pain Research Consortium , Pittsburgh , PA , USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Ignatz
authors.affiliation: d Instituto De Investigaciones Cientificas Y Servicios De Alta Tecnologia (INDICASAT-AIP) , Clayton , Apartado , Panama City, Panama.
authors.forename: Carmenza
authors.initials: C
authors.lastname: Spadafora
authors.affiliation: a Department of Biological Sciences , Duquesne University , Pittsburgh , PA , USA.|b Duquesne University Chronic Pain Research Consortium , Pittsburgh , PA , USA.
authors.forename: Benedict J
authors.initials: BJ
authors.lastname: Kolber
authors.affiliation: b Duquesne University Chronic Pain Research Consortium , Pittsburgh , PA , USA.|c Duquesne University Mylan School of Pharmacy , Pittsburgh , PA , USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tidgewell
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D000458:Cyanobacteria / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011619:Psychotropic Drugs / Q000494:pharmacology*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects*
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D011619:Psychotropic Drugs; D044405:Receptor, Serotonin, 5-HT2C
keywords: Anxiety; GPCR; depression; pain; pharmacognosy