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Cyanobacterial extract with serotonin receptor subtype 7 (5‐HT 7 R) affinity modulates depression and anxiety‐like behavior in mice
Author(s) -
Lax Neil C.,
Parker StacyAnn J.,
Hilton Edward J.,
Seliman Youstina,
Tidgewell Kevin J.,
Kolber Benedict J.
Publication year - 2018
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.22059
Subject(s) - open field , pharmacology , behavioural despair test , serotonin transporter , serotonin , antidepressant , elevated plus maze , receptor , anxiolytic , chemistry , anxiety , psychology , medicine , biochemistry , psychiatry
Marine cyanobacteria represent a unique source in the field of drug discovery due to the secondary metabolites they produce and the structural similarity these compounds have to endogenous mammalian receptor ligands. A series of cyanobacteria were subjected to extraction, fractionation by column chromatography and screened for affinity against CNS targets with a focus on serotonin receptors (5‐HTRs). Out of 276 fractions screened, 21% had activity at 5‐HTRs and/or the 5‐HT transporter (SERT). One sample, a cyanobacterium identified by 16S rRNA sequencing as Leptolyngbya from Las Perlas archipelago in Panama, contained a fraction with noted affinity for the 5‐HT 7 receptor (5‐HT 7 R). This fraction (DUQ0002I) was screened via intracerebroventricular (ICV) injections in mice using depression and anxiety assays including the forced swim, tail suspension, elevated zero maze, and light‐dark preference tests. DUQ0002I decreased depression and anxiety‐like behaviors in males and did not have effects in 5‐HT 7 R knockout or female mice. Administration of DUQ0002I to the CA1 of the hippocampus induced antidepression‐like, but not anxiolytic‐like behaviors. Testing of further purified materials showed no behavioral effects, leading us to hypothesize that the behavioral effects are likely caused by a synergistic effect between multiple compounds in the fraction. Finally, DUQ0002I was used in a model of neuropathic pain with comorbid depression (spared nerve injury—SNI). DUQ0002I had a similar antidepressant effect in animals with SNI, suggesting a role for the 5‐HT 7 R in the development of comorbid pain and depression. These results demonstrate the potential that cyanobacterial metabolites have in the field of neuropharmacognosy.