title: Meclizine enhancement of sensorimotor gating in healthy male subjects with high startle responses and low prepulse inhibition.
abstract: Histamine H1 receptor systems have been shown in animal studies to have important roles in the reversal of sensorimotor gating deficits, as measured by prepulse inhibition (PPI). H1-antagonist treatment attenuates the PPI impairments caused by either blockade of NMDA glutamate receptors or facilitation of dopamine transmission. The current experiment brought the investigation of H1 effects on sensorimotor gating to human studies. The effects of the histamine H1 antagonist meclizine on the startle response and PPI were investigated in healthy male subjects with high baseline startle responses and low PPI levels. Meclizine was administered to participants (n=24) using a within-subjects design with each participant receiving 0, 12.5, and 25 mg of meclizine in a counterbalanced order. Startle response, PPI, heart rate response, galvanic skin response, and changes in self-report ratings of alertness levels and affective states (arousal and valence) were assessed. When compared with the control (placebo) condition, the two doses of meclizine analyzed (12.5 and 25 mg) produced significant increases in PPI without affecting the magnitude of the startle response or other physiological variables. Meclizine also caused a significant increase in overall self-reported arousal levels, which was not correlated with the observed increase in PPI. These results are in agreement with previous reports in the animal literature and suggest that H1 antagonists may have beneficial effects in the treatment of subjects with compromised sensorimotor gating and enhanced motor responses to sensory stimuli.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: José A
authors.initials: JA
authors.lastname: Larrauri
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Lisalynn D
authors.initials: LD
authors.lastname: Kelley
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Mason R
authors.initials: MR
authors.lastname: Jenkins
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Westman
authors.affiliation: Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
authors.forename: Nestor A
authors.initials: NA
authors.lastname: Schmajuk
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA [2] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
authors.forename: M Zachary
authors.initials: MZ
authors.lastname: Rosenthal
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA [2] Department of Psychology and Neuroscience, Duke University, Durham, NC, USA.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Levin
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005712:Galvanic Skin Response / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008468:Meclizine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects* / Q000235:genetics; D057566:Self Report; D055139:Sensory Gating / Q000187:drug effects*; D055815:Young Adult
chemical_list: D006634:Histamine H1 Antagonists; D008468:Meclizine
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