Loudness dependence of auditory evoked potentials as indicator of central serotonergic neurotransmission: simultaneous electrophysiological recordings and in vivo microdialysis in the rat primary auditory cortex

Neuropsychopharmacology. 2008 Dec;33(13):3176-81. doi: 10.1038/npp.2008.42. Epub 2008 May 7.


Serotonin released in synapsis is one of the key neurotransmitters in psychiatry and psychopharmacology. The loudness dependence of auditory evoked potentials (LDAEP) has been proposed as a marker for central serotonergic neurotransmission. Several findings in animals and humans support this hypothesis. However, the in vivo measurement of cortical extracellular serotonin levels has never been performed simultaneously with the recording of auditory evoked potentials. The interrelationship between low cortical serotonergic activity and strong LDAEP is yet to be proven. The auditory evoked potentials were recorded in the epidura above the primary auditory cortex of male Wistar rats whereas extracellular serotonin levels in the primary auditory cortex were measured by in vivo microdialysis before and after i.p. application of the selective serotonin reuptake inhibitor citalopram. At baseline, the correlation of coefficients between the LDAEP, especially of the N1 component, and extracellular serotonin levels in the primary auditory cortex was negative. The increase of serotonin levels after citalopram application was significantly related to a decrease of LDAEP of the N1 component (r=-0.86, p=0.003). These data support the view that the LDAEP is closely modulated by cortical serotonergic activity. Thus, the LDAEP might serve as an inversely related marker of synaptically released serotonin in the CNS.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Cortex / drug effects
  • Auditory Cortex / metabolism*
  • Auditory Pathways / drug effects
  • Auditory Pathways / metabolism
  • Citalopram / pharmacology
  • Electrophysiology
  • Evoked Potentials, Auditory / drug effects
  • Evoked Potentials, Auditory / physiology*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Loudness Perception / drug effects
  • Loudness Perception / physiology*
  • Male
  • Microdialysis
  • Neurons / drug effects
  • Neurons / metabolism*
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Serotonin