The effects of DHBE and MLA on nicotine-induced enhancement of contextual fear conditioning in C57BL/6 mice |
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Authors: | Jennifer A Davis Thomas J Gould |
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Institution: | (1) Neuroscience Program, Temple University, Philadelphia, PA, USA;(2) Department of Psychology, Weiss Hall, Temple University, Philadelphia, PA 19122, USA |
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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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Keywords: | Dihydro-beta-erythroidine Methyllycaconitine Nicotinic receptors Learning Hippocampus Mice |
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