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


OBJECTIVE
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 alpha7 nAChR antagonist methyllycaconitine (MLA; 1.00, 10.00, and 20.00 mg/kg) and the effects of the alpha4beta2 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-alpha7 nAChRs (most likely alpha4beta2 nAChRs) underlie the enhancement of contextual fear conditioning by nicotine.
Neuroscience Program, Temple University, Philadelphia, PA 19122, USA.
Jennifer A
JA
Davis
Thomas J
TJ
Gould
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005239:Fear / Q000187:drug effects*; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*
D000157:Aconitine; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D011978:Receptors, Nicotinic; C054634:methyllycaconitine