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

Abstract

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 ¼ À0.86, p ¼ 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.

Chronic modulation of serotonergic neurotransmission with sertraline attenuates the loudness dependence of the auditory evoked potential in healthy participants

“…Furthermore, these findings support previous studies demonstrating a relationship between higher central serotonergic functioning and a weaker LDAEP (e.g. Juckel et al 1997;Wutzler et al 2008). The current findings were not moderated by either gender or 5-HTTLRP genotype, and plasma drug levels did not correlate with the LDAEP in the sertraline group.…”

“…For example, in vivo microdialysis studies have revealed that 5-HT levels in the primary auditory cortex modulate the LDAEP in animals (Juckel et al 1997;Wutzler et al 2008). Further, an altered LDAEP has been demonstrated in psychiatric disorders (and some subtypes) where the serotonergic system is implicated, including major depressive disorder (Fitzgerald et al 2009;Park et al 2010), schizophrenia (Juckel et al 2008a;Gudlowski et al 2009;Park et al 2010) and bipolar disorder (Park et al 2010).…”

“…only a small increase in the evoked cortical response with increasing intensity of the stimuli (see Hegerl et al 2001). The primary and not secondary auditory cortex is the focus, as the primary auditory cortex has been found be densely innervated with serotonergic projections (see Hegerl et al 2001), and has been reported to be the primary source of the LDAEP identified by concurrent fMRI and EEG in humans (Mulert et al 2005) and by in vivo agonist/antagonist drug manipulations in animal studies (Juckel et al 1996(Juckel et al , 1997(Juckel et al , 1999Wutzler et al 2008).…”

“…The loudness (or intensity) dependence of the auditory evoked potential (LDAEP) has been reported to be an effective, non-invasive biomarker of central serotonergic function in healthy adults (Hegerl et al 1994;O'Neill et al 2008a, b) and animals (Juckel et al 1997;Wutzler et al 2008). For example, in vivo microdialysis studies have revealed that 5-HT levels in the primary auditory cortex modulate the LDAEP in animals (Juckel et al 1997;Wutzler et al 2008).…”

How Human Electrophysiology Informs Psychopharmacology: from Bottom-up Driven Processing to Top-Down Control

“…For example, Juckel et al (1999) reported differential effects of microinjection of a 5-HT 1A agonist and a 5-HT 1A antagonist into the dorsal raphe nucleus on the intensity dependence of auditory evoked potentials recorded epidurally from the primary and secondary auditory cortex in behaving cats. Futhermore, Wutzler et al, 2008 showed that the increase of serotonin levels after citalopram application in rats was significantly related to a decrease of LDAEP of the N1 component.…”