beta2 subunit-containing nicotinic receptors mediate the enhancing effect of nicotine on trace cued fear conditioning in C57BL/6 mice.
BACKGROUND
Previous research indicates that acute nicotine administration enhances the acquisition of contextual fear conditioning and trace cued fear conditioning. Pharmacological inhibition of alpha4beta2 nicotinic acetylcholine receptors (nAChRs), but not alpha7 nAChRs, blocked the enhancing effect of nicotine on contextual fear conditioning. Similarly, genetic deletion of the beta2 nAChR subunit but not the alpha7 nAChR subunit blocked the enhancing effect of nicotine on contextual fear conditioning.


OBJECTIVE
In the present study, nAChR subunit knockout mice were used to compare the involvement of beta2 subunit-containing nAChRs and alpha7 subunit-containing nAChRs in the effects of nicotine on hippocampus-dependent trace cued fear conditioning and contextual fear conditioning.


METHODS
beta2 nAChR subunit knockout mice, alpha7 nAChR subunit knockout mice, and their wild-type littermates received either nicotine or saline 5 minutes before training and testing. Mice were trained using five conditioned stimulus (CS; 30 s, 85 dB white noise)--trace (30 s)--unconditioned stimulus (US; 2 s footshock) pairings. Freezing to the context and freezing to the CS were assessed 24 h later.


RESULTS
Both contextual and trace cued fear conditioning were enhanced by nicotine administration in wild-type littermates and in alpha7 nAChR subunit knockout mice. In contrast, neither contextual fear conditioning nor trace cued fear conditioning was enhanced by nicotine administration in beta2 nAChR subunit knockout mice.


CONCLUSIONS
These results suggest that beta2 subunit-containing nAChRs but not alpha7 nAChR subunit-containing nAChRs are critically involved in the enhancing effect of nicotine on contextual and trace cued fear conditioning.
Davis
Jennifer A
JA
Department of Psychology, Weiss Hall, Temple University, Philadelphia, PA, 19122, USA.
Gould
Thomas J
TJ
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000523:psychology*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor
D009538:Nicotine; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C579166:Chrna7 protein, mouse; C403531:nicotinic receptor alpha4beta2