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The effects of DHBE and MLA on nicotine-induced enhancement of contextual fear conditioning in C57BL/6 mice

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Abstract

Rationale

Previous research indicates that nicotine administration enhances hippocampus-dependent forms of learning, including contextual fear conditioning. This effect is blocked by mecamylamine, a noncompetitive, broad-spectrum nicotinic receptor antagonist.

Objectives

The present study extends previous research by further characterizing the nicotinic acetylcholinergic receptor (nAChR) subtypes through which nicotine acts to enhance contextual fear conditioning.

Methods

C57BL/6J mice were trained with two conditioned stimulus (CS; 30 s, 85-dB white noise)–unconditioned stimulus (US; 2 s, 0.57-mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. The effects of the α7 nAChR antagonist methyllycaconitine (MLA; 1.00, 10.00, and 20.00 mg/kg) and the effects of the α4β2 nAChR antagonist dihydro-beta-erythroidine (DHBE; 1.00, 3.00, and 6.00 mg/kg) on cued and contextual fear conditioning and on the enhancement of contextual fear conditioning by nicotine (0.25 mg/kg) were examined.

Results

We demonstrate that DHBE (all doses) administration attenuates the enhancing effect of nicotine on contextual fear conditioning, and MLA administration has no significant effect on the enhancement of contextual fear conditioning by nicotine.

Conclusions

The data suggest that non-α7 nAChRs (most likely α4β2 nAChRs) underlie the enhancement of contextual fear conditioning by nicotine.

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Acknowledgements

The authors would like to acknowledge grant support from the American Federation for Aging Research (TG), the Pennsylvania Department of Health (TG), and Temple University (TG).

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  1. Neuroscience Program, Temple University, Philadelphia, PA, USA

    Jennifer A. Davis & Thomas J. Gould

  2. Department of Psychology, Weiss Hall, Temple University, Philadelphia, PA, 19122, USA

    Thomas J. Gould

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  1. Jennifer A. Davis
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Correspondence to Thomas J. Gould.

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Davis, J.A., Gould, T.J. The effects of DHBE and MLA on nicotine-induced enhancement of contextual fear conditioning in C57BL/6 mice. Psychopharmacology 184, 345–352 (2006). https://doi.org/10.1007/s00213-005-0047-y

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