Role of nicotinic receptors in the lateral habenula in the attenuation of amphetamine-induced prepulse inhibition deficits of the acoustic startle response in rats

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• 作者：José A. Larrauri ; Dennis A. Burke ; Brandon J. Hall ; Edward D. Levin
• 关键词：Prepulse inhibition ; Nicotine ; Amphetamine ; Dizocilpine ; Habenula ; Nicotinic receptors
• 刊名：Psychopharmacology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：232
• 期：16
• 页码：3009-3017
• 全文大小：367 KB
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• 作者单位：José A. Larrauri (1)
  Dennis A. Burke (1)
  Brandon J. Hall (1)
  Edward D. Levin (1)
  
  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box #104790, Durham, NC, 27710, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Psychiatry
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-2072

文摘

Rationale Prepulse inhibition (PPI) refers to the reduction of the startle response magnitude when a startling stimulus is closely preceded by a weak stimulus. PPI is commonly used to measure sensorimotor gating. In rats, the PPI reduction induced by the dopamine agonist apomorphine can be reversed by systemic administration of nicotine. A high concentration of nicotinic receptors is found in the lateral habenula (LHb), an epithalamic structure with efferent projections to brain regions involved in the modulation of PPI, which has been shown to regulate the activity of midbrain dopamine neurons. Objectives The prospective role of nicotinic receptors in the LHb in the regulation of PPI was assessed in this study, using different pharmacological models of sensorimotor gating deficits. Methods Interactions between systemic amphetamine and haloperidol and intra-LHb infusions of mecamylamine (10?μg/side) or nicotine (30?μg/side) on PPI were analyzed in Experiments 1 and 2. Intra-LHb infusions of different nicotine doses (25, and 50?μg/side) and their interactions with systemic administration of amphetamine or dizocilpine on PPI were examined in Experiments 3 and 4. Results Infusions of nicotine into the LHb dose-dependently attenuated amphetamine-induced PPI deficits but had no effect on PPI disruptions caused by dizocilpine. Intra-LHb mecamylamine infusions did not affect PPI nor interact with dopaminergic manipulations. Conclusions These results are congruent with previous reports of systemic nicotine effects on PPI, suggesting a role of the LHb in the attenuation of sensorimotor gating deficits caused by the hyperactivity of dopamine systems.