Nicotine withdrawal-induced deficits in trace fear conditioning in C57BL/6 mice - a role for high-affinity beta 2 subunit-containing nicotinic acetylcholine receptors

作者：Raybuck J D; Gould T J^*

来源：European Journal of Neuroscience, 2009, 29(2): 377-387.

DOI：10.1111/j.1460-9568.2008.06580.x

• addiction
• cognition
• hippocampus
• learning
• working memory

Nicotine alters cognitive processes that include working memory and long-term memory. Trace fear conditioning may involve working memory during acquisition while also allowing the assessment of long-term memory. The present study used trace fear conditioning in C57BL/6 mice to investigate the effects of acute nicotine, chronic nicotine and withdrawal of chronic nicotine on processes active during acquisition and recall 24 h later and to examine the nicotinic acetylcholine receptor subtypes (nAChRs) involved in withdrawal deficits in trace fear conditioning. During training, acute nicotine (0.09 mg/kg) enhanced, but chronic nicotine (6.3 mg/kg/day, 13 days) and withdrawal of chronic nicotine (6.3 mg/kg/day, 12 days) had no significant effect on, acquisition of trace conditioning. At recall, acute treatment enhanced conditioning while chronic nicotine had no effect and withdrawal of chronic nicotine resulted in deficits. Antagonist-precipitated withdrawal was used to characterize the nAChRs involved in the withdrawal deficits. The low-affinity nAChR antagonist MLA (1.5, 3 or 9 mg/kg) had no effect on trace fear conditioning, but the high-affinity nAChR antagonist DH beta E (3 mg/kg) precipitated deficits in trace fear conditioning if administered at training or training and testing, but not if administered at testing alone. The beta 2 nAChR subunit is involved in the withdrawal effects as withdrawal of chronic nicotine produced deficits in trace fear conditioning in wildtype but not in beta 2-knockout mice. Thus, nicotine alters processes involved in both acquisition and long-term memory of trace fear conditioning, and high-affinity beta 2 subunit-containing nAChRs are critically involved in the effects of nicotine withdrawal on trace fear conditioning.

• 出版日期2009-1