Hyperforin enhances the extracellular concentrations of catecholamines, serotonin and glutamate in the rat locus coeruleus

Neurosci Lett. 1999 Mar 12;262(3):199-202. doi: 10.1016/s0304-3940(99)00087-7.


Hyperforin is the main antidepressant component of hypericum perforatum (St. John's Wort). Using the push-pull superfusion technique we tested whether hyperforin influences extracellular concentrations of neurotransmitters in the rat locus coeruleus. Hyperforin (10 mg/kg, i.p.) not only enhanced the extracellular levels of the monoamines dopamine, noradrenaline and serotonin, but also that of the excitatory amino acid glutamate. The levels of the main serotonin metabolite 5-hydroxyindolacetic acid, as well as those of the amino acids GABA, taurine, aspartate, serine and arginine, were not influenced. Together with in vitro studies, our findings suggest that the antidepressant property of hyperforin is due to enhanced concentrations of monoamines and glutamate in the synaptic cleft, probably as a consequence of uptake inhibition.

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bridged Bicyclo Compounds
  • Catecholamines / metabolism*
  • Dopamine / metabolism
  • Extracellular Space
  • Glutamic Acid / metabolism*
  • Hydroxyindoleacetic Acid / metabolism
  • Kinetics
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / physiology*
  • Male
  • Norepinephrine / metabolism
  • Phloroglucinol / analogs & derivatives
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Terpenes / pharmacology
  • gamma-Aminobutyric Acid / metabolism


  • Amino Acids
  • Anti-Bacterial Agents
  • Bridged Bicyclo Compounds
  • Catecholamines
  • Terpenes
  • Serotonin
  • Glutamic Acid
  • Hydroxyindoleacetic Acid
  • gamma-Aminobutyric Acid
  • Phloroglucinol
  • hyperforin
  • Dopamine
  • Norepinephrine