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.
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References
Aasen I, Kolli L, Kumari V (2005). Sex effects in prepulse inhibition and facilitation of the acoustic startle response: implications for pharmacological and treatment studies. J Psychopharmacol 19: 39–45.
Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E (1998). Effects of bromocriptine and haloperidol on prepulse inhibition of the acoustic startle response in man. J Psychopharmacol 12: 239–245.
Abel KM, Allin MP, Hemsley DR, Geyer MA (2003). Low dose ketamine increases prepulse inhibition in healthy men. Neuropharmacology 44: 729–737.
Blumenthal TD, Cuthbert BN, Filion DL, Hackley S, Lipp OV, van Boxtel A (2005). Committee report: guidelines for human startle eyeblink electromyographic studies. Psychophysiology 42: 1–15.
Braff DL (1993). Information processing and attention dysfunctions in schizophrenia. Schizophr Bull 19: 233–259.
Braff DL, Geyer MA, Swerdlow NR (2001). Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology (Berlin) 156: 234–258.
Braff DL, Grillon C, Geyer MA (1992). Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49: 206–215.
Braff DL, Stone C, Callaway E, Geyer MA, Glick I, Bali L (1978). Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15: 339–343.
Braff DL, Swerdlow NR, Geyer MA (1999). Symptom correlates of prepulse inhibition deficits in male schizophrenic patients. Am J Psychiatry 156: 596–602.
Braff DL, Geyer MA (1990). Sensorimotor gating and schizophrenia: human and animal model studies. Arch Gen Psychiatry 47: 181–188.
Bundgaard C, Larsen F, Jørgensen M, Gabrielsson J (2006). Mechanistic model of acute autoinhibitory feedback action after administration of SSRIs in rats: application to escitalopram-induced effects on brain serotonin levels. Eur J Pharm Sci 29: 394–404.
Cadenhead KS (2002). Vulnerability markers in the schizophrenia spectrum: implications for phenomenology, genetics, and the identification of the schizophrenia prodrome. Psychiatr Clin North Am 25: 837–853.
Cadenhead KS, Swerdlow NR, Shafer KM, Diaz M, Braff DL (2000). Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry 157: 1660–1668.
Christoffersen GR (1997). Habituation: events in the history of its characterization and linkage to synaptic depression. A new proposed kinetic criterion for its identification. Prog Neurobiol 53: 45–66.
Dulawa SC, Geyer MA (2000). Effects of strain and serotonergic agents on prepulse inhibition and habituation in mice. Neuropharmacology 39: 2170–2179.
Dulawa SC, Hen R, Scearce Levie K, Geyer MA (1997). Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse inhibition in wild-type and serotonin1B knockout mice. Psychopharmacology (Berlin) 132: 125–134.
Duncan E, Szilagyi S, Schwartz M, Kunzova A, Negi S, Efferen T et al (2003a). Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol. Psychiatry Res 120: 1–12.
Duncan EJ, Szilagyi S, Efferen TR, Schwartz MP, Parwani A, Chakravorty S et al (2003b). Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia. Psychopharmacology (Berlin) 167: 63–71.
Geyer MA, Braff DL (1982). Habituation of the blink reflex in normals and schizophrenic patients. Psychophysiology 19: 1–6.
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001). Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology (Berlin) 156: 117–154.
Geyer MA, Swerdlow NR, Mansbach RS, Braff DL (1990). Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res Bull 25: 485–498.
Geyer MA, Tapson GS (1988). Habituation of tactile startle is altered by drugs acting on serotonin-2 receptors. Neuropsychopharmacology 1: 135–147.
Gouzoulis-Mayfrank E, Heekeren K, Thelen B, Lindenblatt H, Kovar KA, Sass H et al (1998). Effects of the hallucinogen psilocybin on habituation and prepulse inhibition of the startle reflex in humans. Behav Pharmacol 9: 561–566.
Graham FK (1975). The more or less startling effects of weak prestimulation. Psychophysiology 12: 238–248.
Gutierrez MM, Abramowitz W (2000). Pharmacokinetic comparison of oral solution and tablet formulations of citalopram: a single-dose, randomized, crossover study. Clin Ther 22: 1525–1532.
Hammer TB, Oranje B, Glenthoj B (2007). The effects of imipramine on P50 suppression, prepulse inhibition and habituation of the startle response in humans. Int J Neuropsychopharmacol 25: 1–9.
Jovanovic T, Szilagyi S, Chakravorty S, Fiallos AM, Lewison BJ, Parwani A et al (2004). Menstrual cycle phase effects on prepulse inhibition of acoustic startle. Psychophysiology 41: 401–406.
Kumari V, Aasen I, Sharma T (2004). Sex differences in prepulse inhibition deficits in chronic schizophrenia. Schizophr Res 69: 219–235.
Kumari V, Antonova E, Geyer MA, ffytche D, Williams SC, Sharma T (2006). A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics. Int J Neuropsychopharmacol 1–15.
Kumari V, Sharma T (2002). Effects of typical and atypical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research. Psychopharmacology (Berlin) 162: 97–101.
Kumari V, Soni W, Mathew VM, Sharma T (2000). Prepulse inhibition of the startle response in men with schizophrenia—effects of age of onset of illness, symptoms, and medication. Arch Gen Psychiatry 57: 609–614.
Kumari V, Soni W, Sharma T (1999). Normalization of information processing deficits in schizophrenia with clozapine. Am J Psychiatry 156: 1046–1051.
Kumari V, Soni W, Sharma T (2002). Prepulse inhibition of the startle response in risperidone-treated patients: comparison with typical antipsychotics. Schizophr Res 55: 139–146.
Liechti ME, Geyer MA, Hell D, Vollenweider FX (2001). Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin. Neuropsychopharmacology 24: 240–252.
Ludewig K, Geyer MA, Etzensberger M, Vollenweider FX (2002). Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia. Schizophr Res 55: 129–137.
Ludewig K, Geyer MA, Vollenweider FX (2003). Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia. Biol Psychiatry 54: 121–128.
Mackeprang T, Kristiansen KT, Glenthoj BY (2002). Effects of antipsychotics on prepulse inhibition of the startle response in drug-naive schizophrenic patients. Biol Psychiatry 52: 863–873.
Meincke U, Light GA, Geyer MA, Braff DL, Gouzoulis-Mayfrank E (2004). Sensitization and habituation of the acoustic startle reflex in patients with schizophrenia. Psychiatry Res 126: 51–61.
Meltzer HY, Li Z, Kaneda Y, Ichikawa J (2003). Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27: 1159–1172.
Metting van Rijn AC, Kuiper AP, Dankers TE, Grimbergen CA (1996). Low-cost active electrode improves the resolution in biopotential recordings. Proceedings of the 18th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Amsterdam, The Netherlands, Track 1 2 3-3.
Nadeem HS, Attenburrow MJ, Cowen PJ (2004). Comparison of the effects of citalopram and escitalopram on 5-Ht-mediated neuroendocrine responses. Neuropsychopharmacology 29: 1699–1703.
Oranje B, Gispen-de Wied CC, Verbaten MN, Kahn RS (2002a). Modulating sensory gating in healthy volunteers. The effects of ketamine and haloperidol. Biol Psychiatry 52: 887–895.
Oranje B, Jensen KS, Wienberg M, Glenthoj BY . The effects of increased serotonergic activity on psychophysiological parameters of human selective attention (submitted).
Oranje B, Oel CJ, Gispen-de Wied CC, Verbaten MN, Kahn RS (2002b). Effects of typical and atypical antipsychotics on the prepulse inhibition of the startle reflex in patients with schizophrenia. J Clin Psychopharmacol 4: 359–365.
Oranje B, Verbaten MN, Kemner C, Kahn RS (2004). Modulating sensorimotor gating in healthy volunteers: the effects of desipramine and haloperidol. Psychiatry Res 127: 195–205.
Parwani A, Duncan EJ, Bartlett E, Madonick SH, Efferen TR, Rajan R et al (2000). Impaired prepulse inhibition of acoustic startle in schizophrenia. Biol Psychiatry 47: 662–669.
Perry W, Feifel D, Minassian A, Bhattacharjie I, Braff DL (2002). Information processing deficits in acutely psychotic schizophrenia patients medicated and unmedicated at the time of admission. Am J Psychiatry 159: 1375–1381.
Perry W, Geyer MA, Braff DL (1999). Sensorimotor gating and thought disturbance measured in close temporal proximity in schizophrenic patients. Arch Gen Psychiatry 56: 277–281.
Phillips MA, Langley RW, Bradshaw CM, Szabadi E (2000). The effects of some antidepressant drugs on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man. J Psychopharmacol 14: 40–45.
Quednow BB, Kuhn KU, Stelzenmueller R, Hoenig K, Maier W, Wagner M (2004). Effects of serotonergic and noradrenergic antidepressants on auditory startle response in patients with major depression. Psychopharmacology (Berlin) 175: 399–406.
Riba J, Rodriguez-Fornells A, Barbanoj MJ (2002). Effects of ayahuasca on sensory and sensorimotor gating in humans as measured by P50 suppression and prepulse inhibition of the startle reflex, respectively. Psychopharmacology (Berlin) 165: 18–28.
Rigdon GC, Weatherspoon JK (1992). 5-Hydroxytryptamine 1a receptor agonists block prepulse inhibition of acoustic startle reflex. J Pharmacol Exp Ther 263: 486–493.
Swerdlow NR, Auerbach P, Monroe SM, Hartston H, Geyer MA, Braff DL (1993). Men are more inhibited than women by weak prepulses. Biol Psychiatry 34: 253–260.
Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994). Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51: 139–154.
Swerdlow NR, Geyer MA, Hartman PL, Sprock J, Auerbach PP, Cadenhead K et al (1999). Sex differences in sensorimotor gating of the human startle reflex: all smoke? Psychopharmacology (Berlin) 146: 228–232.
van Berckel BN, Oranje B, van Ree JM, Verbaten MN, Kahn RS (1998). The effects of low dose ketamine on sensory gating, neuroendocrine secretion and behavior in healthy human subjects. Psychopharmacology (Berlin) 137: 271–281.
Vollenweider FX, Remensberger S, Hell D, Geyer MA (1999). Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans. Psychopharmacology (Berlin) 143: 365–372.
Wing JK, Babor T, Brugha T, Burke J, Cooper JE, Giel R et al (1990). SCAN. Schedules for Clinical Assessment in Neuropsychiatry. Arch Gen Psychiatry 47: 589–593.
Acknowledgements
This study was supported by an unrestricted grant from the Lundbeck foundation and by the Faculty of health Sciences from the University of Copenhagen. Furthermore, the study was approved by the Committee for Biomedical Research Ethics Copenhagen, and therefore complies with the current laws regarding experimental research of Denmark.
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Jensen, K., Oranje, B., Wienberg, M. et al. The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response. Neuropsychopharmacol 32, 2117–2124 (2007). https://doi.org/10.1038/sj.npp.1301350
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DOI: https://doi.org/10.1038/sj.npp.1301350
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