Meclizine enhancement of sensorimotor gating in healthy male subjects with high startle responses and low prepulse inhibition.
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2014-02
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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.
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Larrauri, José A, Lisalynn D Kelley, Mason R Jenkins, Eric C Westman, Nestor A Schmajuk, M Zachary Rosenthal and Edward D Levin (2014). Meclizine enhancement of sensorimotor gating in healthy male subjects with high startle responses and low prepulse inhibition. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 39(3). pp. 651–659. 10.1038/npp.2013.248 Retrieved from https://hdl.handle.net/10161/31298.
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Scholars@Duke
Eric Charles Westman
Dr. Westman is an Associate Professor of Medicine at Duke University. He is Board Certified in Obesity Medicine and Internal Medicine, and founded the Duke Keto Medicine Clinic with Dr. William S. Yancy Jr. in 2006 after 8 years of clinical research regarding low carbohydrate ketogenic diets.
He is Past-President and Master Fellow of the Obesity Medicine Association and Fellow of The Obesity Society. He is an editor of the textbook: Obesity: Evaluation & Treatment Essentials, and author of the New York Times Bestseller The New Atkins for a New You, Cholesterol Clarity, and Keto Clarity. He is co-founder of Adapt Your Life, an education and product company based on low carbohydrate concepts.
He is course coordinator for MED415c, a Fourth-Year Medical Student Elective on the Medical Management of Obesity, and a faculty member of the Duke Clinical Research Training Program.
Mark Zachary Rosenthal
Misophonia, emotional functioning, borderline personality disorder, virtual reality, digital health, behavioral therapies, cognitive behavioral therapy (CBT) and dialectical behavior therapy (DBT)
Edward Daniel Levin
Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.
The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.
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