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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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Abstract

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.

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Acknowledgments

This research was sponsored by the Wallace Research Foundation. Supported by NIDA P50 grant DA027840.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box #104790, Durham, NC, 27710, USA

    José A. Larrauri, Dennis A. Burke, Brandon J. Hall & Edward D. Levin

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  1. José A. Larrauri
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  2. Dennis A. Burke
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  3. Brandon J. Hall
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  4. Edward D. Levin
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Correspondence to Edward D. Levin.

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Larrauri, J.A., Burke, D.A., Hall, B.J. et al. Role of nicotinic receptors in the lateral habenula in the attenuation of amphetamine-induced prepulse inhibition deficits of the acoustic startle response in rats. Psychopharmacology 232, 3009–3017 (2015). https://doi.org/10.1007/s00213-015-3940-z

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