The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Abstract

Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.

Differential Effects of Acute Serotonin and Dopamine Depletion on Prepulse Inhibition and P50 Suppression Measures of Sensorimotor and Sensory Gating in Humans

“…The findings also concur with a number of studies that report the opposite effect (ie an increase in PPI with enhancement of serotonergic neurotransmission) with MDMA (Liechti et al, 2001) and the 5-HT 2A/1A agonist psilocybin (Gouzoulis-Mayfrank et al, 1998;Vollenweider et al, 1999). However, serotonergic manipulation has not consistently modulated PPI in all studies in humans, with some studies reporting no effects on PPI following acute enhancement of synaptic serotonin with the serotonin reuptake inhibitors, fenfluramine (Abel et al, 2007), fluvoxamine (Phillips et al, 2000b), citalopram (Liechti et al, 2001), and escitalopram (Jensen et al, 2007); and other studies reporting a reduction in PPI or no effects on PPI (depending on the ISI) with psilocybin (Vollenweider et al, 2007). While the reason for this inconsistency is unclear, there are some important possibilities worth discussing.…”

“…On the other hand, reducing serotonergic neurotransmission with ketanserin (a non-selective 5-HT 2 receptor antagonist) (Graham et al, 2002) or buspirone (a 5-HT 1A partial agonist acting presynaptically) (Gogos et al, 2006) has been found to reduce PPI. Nevertheless, other studies have found no effects on PPI following enhancement of central serotonin levels with the administration of serotonin reuptake inhibitors, fenfluramine (Abel et al, 2007), fluvoxamine (Phillips et al, 2000b), citalopram (Liechti et al, 2001), and escitalopram (Jensen et al, 2007). To our knowledge, the effects of serotonergic modulation on P50 suppression in healthy humans has only been investigated once, with findings showing a decrease in P50 suppression with the psychedelic plant ayahuasca, which contains many active constituents including N,N-dimethyltryptamine, a 5-HT 2A/2C receptor agonist (Riba et al, 2002).…”

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive, First-Episode Schizophrenia Patients

“…Both PPI and P50 gating paradigms have been described previously Jensen et al, 2007). Briefly, all auditory stimuli were presented by a computer running Presentation (Neurobehavioral Systems, Albany, NY) software and were presented binaurally through stereo D2 blockade, sensory, and sensorimotor gating in schizophrenia S Düring et al insert earphones (Eartone-ABR, C and H Distributors, Milwaukee, WI).…”

Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women

“…Yet no effect of SSRI on PPI has been demonstrated (e.g. (Jensen et al, 2007;Phillips et al, 2000)), thus, interpretation of the present finding should be cautious and call for further studies on chronic serotonergic modulation of PPI.…”