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. 2017 Nov:145:143-150.
doi: 10.1016/j.nlm.2017.10.002. Epub 2017 Oct 7.

Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity

Munir Gunes Kutlu  1 , Brendan Garrett  2 , Sana Gadiwalla  3 , Jessica M Tumolo  2 , Thomas J Gould  3
Affiliations

Acute nicotine disrupts consolidation of contextual fear extinction and alters long-term memory-associated hippocampal kinase activity

Munir Gunes Kutlu et al. Neurobiol Learn Mem. 2017 Nov.

Abstract

Previous research has shown that acute nicotine, an agonist of nAChRs, impaired fear extinction. However, the effects of acute nicotine on consolidation of contextual fear extinction memories and associated cell signaling cascades are unknown. Therefore, we examined the effects of acute nicotine injections before (pre-extinction) and after (post-extinction) contextual fear extinction on behavior and the phosphorylation of dorsal and ventral hippocampal ERK1/2 and JNK1 and protein levels on the 1st and 3rd day of extinction. Our results showed that acute nicotine administered prior to extinction sessions downregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but not dorsal hippocampus, and JNK1 in both dorsal and ventral hippocampus on the 3rd extinction day. These effects were absent on the 1st day of extinction. We also showed that acute nicotine administered immediately and 30 min, but not 6 h, following extinction impaired contextual fear extinction suggesting that acute nicotine disrupts consolidation of contextual fear extinction memories. Finally, acute nicotine injections immediately after extinction sessions upregulated the phosphorylated forms of ERK1/2 in the ventral hippocampus, but did not affect JNK1. These results show that acute nicotine impairs contextual fear extinction potentially by altering molecular processes responsible for the consolidation of extinction memories.

Keywords: ERK1/2; Extinction; Hippocampus; JNK1; Nicotine.

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Conflict of interest statement

We declare no potential conflict of interest.

Figures

Figure 1
Figure 1. Acute nicotine injections prior to extinction sessions disrupt contextual fear extinction during the 3rd extinction day, but not 1st extinction day
Panel A: Mice administered acute nicotine (0.18 mg/kg) did not show impaired contextual fear extinction during the 1st extinction day (n=7-8 per group). Panel B: Acute nicotine (0.18 mg/kg) administered mice showed impaired contextual fear extinction during the 2nd and 3rd extinction days (n=7 per group). Error bars indicate Standard Error of the Mean (SEM). (*) denotes significant differences between nicotine group and saline controls at the p<0.05 level.
Figure 2
Figure 2. Acute nicotine injections prior to extinction sessions downregulate the active form of ERK1/2 in the ventral hippocampus at the 3rd, but not 1st extinction day
Panel A: Acute nicotine (0.18 mg/kg) administration prior to extinction did not have an effect on pERK/tERK ratio in dHPC and vHPC on the 1st extinction day (n=7-8 per group). Panel B: Acute nicotine (0.18 mg/kg) administration prior to extinction downregulated vHPC pERK/tERK ratio but did not have an effect on dHPC pERK/tERK ratio on the 3rd extinction day. Error bars indicate Standard Error of the Mean (SEM). (*) denotes significant differences between nicotine group and saline controls at the p<0.05 level.
Figure 3
Figure 3. Acute nicotine injections prior to extinction sessions downregulate the active form of JNK1 in the dorsal and ventral hippocampus at the 3rd, but not 1st extinction day
Panel A: Acute nicotine (0.18 mg/kg) administration prior to extinction did not have an effect on pJNK1/tJNK ratio in dHPC and vHPC at the 1st extinction day (n=7-8 per group). Panel B: Acute nicotine (0.18 mg/kg) administration prior to extinction downregulated both dHPC and vHPC pJNK1/tJNK ratio at the 3rd extinction day. Error bars indicate Standard Error of the Mean (SEM). (*) denotes significant differences between nicotine group and saline controls at the p<0.05 level.
Figure 4
Figure 4. Acute nicotine administered following extinction sessions disrupts consolidation of contextual fear extinction memories
Panel A: Acute nicotine (0.18 mg/kg) administered immediately following extinction sessions disrupted consolidation of contextual fear extinction in mice (n=8-10 per group). Panel B: Acute nicotine (0.18 mg/kg) administered 30 mins after extinction sessions disrupted consolidation of contextual fear extinction in mice (n=9-10 per group). Panel C: Acute nicotine (0.18 mg/kg) administered 6 hrs after extinction sessions had no effects on consolidation of contextual fear extinction in mice (n=7-8 per group). Error bars indicate Standard Error of the Mean (SEM). (*) denotes significant differences between nicotine group and saline controls at the p<0.05 level.
Figure 5
Figure 5. Acute nicotine injections following extinction sessions upregulate the active form of ERK1/2 in the ventral hippocampus but have no effect on JNK1 phosphorylation
Panel A: Acute nicotine (0.18 mg/kg) administered immediately following extinction sessions disrupted consolidation of contextual fear extinction in mice (n=7-8 per group). Panel B: Acute nicotine (0.18 mg/kg) administration following extinction sessions resulted in increased pERK/tERK ratio in the ventral, but not in dorsal, hippocampus (n=7-8 per group). Panel C: Acute nicotine (0.18 mg/kg) administration immediately following extinction sessions had no effect on pJNK1/tJNK ratio in the dorsal and ventral hippocampus (n=7-8 per group). Error bars indicate Standard Error of the Mean (SEM). (*) denotes significant differences between nicotine group and saline controls at the p<0.05 level.
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