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Strain dependency of the effects of nicotine and mecamylamine in a rat model of attention

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Abstract

Rationale

Processes of attention have a heritable component, suggesting that genetic predispositions may predict variability in the response to attention-enhancing drugs. Among lead compounds with attention-enhancing properties are nicotinic acetylcholine receptor (nAChR) agonists.

Objectives

This study aims to test, by comparing three rat strains, whether genotype may influence the sensitivity to nicotine in the 5-choice serial reaction time task (5-CSRTT), a rodent model of attention.

Methods

Strains tested were Long Evans (LE), Sprague Dawley (SD), and Wistar rats. The 5-CSRTT requires responses to light stimuli presented randomly in one of five locations. The effect of interest was an increased percentage of responses in the correct location (accuracy), the strongest indicator of improved attention.

Results

Nicotine (0.05–0.2 mg/kg s.c.) reduced omission errors and response latency and increased anticipatory responding in all strains. In contrast, nicotine dose-dependently increased accuracy in Wistar rats only. The nAChR antagonist mecamylamine (0.75–3 mg/kg s.c.) increased omissions, slowed responses, and reduced anticipatory responding in all strains. There were no effects on accuracy, which was surprising giving the clear improvement with nicotine in the Wistar group.

Conclusions

The findings suggest strain differences in the attention-enhancing effects of nicotine, which would indicate that genetic predispositions predict variability in the efficacy of nAChR compounds for enhancing attention. The absence of effect of mecamylamine on response accuracy may suggest a contribution of nAChR desensitization to the attention-enhancing effects of nicotine.

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Acknowledgments

We thank Dr. Ian Stolerman for insightful comments on this manuscript.

Funding and disclosure

This work was supported by a grant from the National Institute on Drug Abuse (grant number R01 DA035813 to B.H.). The authors have no competing financial interests in relation to the work described and no financial relationship with the organization that sponsored the research. The authors have full control of all primary data and agree to allow the journal to review the data if requested.

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Authors and Affiliations

  1. University of Maryland School of Medicine, Maryland Psychiatric Research Center, P.O. Box 21247, Baltimore, MD, 21228, USA

    Britta Hahn, Katelyn E. Riegger & Greg I. Elmer

Authors
  1. Britta Hahn
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  2. Katelyn E. Riegger
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  3. Greg I. Elmer
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Corresponding author

Correspondence to Britta Hahn.

Ethics declarations

The treatment of animals followed the “Principles of Laboratory Animal Care” (NIH publication no. 86-23, 1996) and was approved by the Institutional Animal Care and Use Committee of the University of Maryland School of Medicine.

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Hahn, B., Riegger, K.E. & Elmer, G.I. Strain dependency of the effects of nicotine and mecamylamine in a rat model of attention. Psychopharmacology 233, 1427–1434 (2016). https://doi.org/10.1007/s00213-016-4236-7

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  • DOI: https://doi.org/10.1007/s00213-016-4236-7

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