Journal
JOURNAL OF NEUROSCIENCE
Volume 25, Issue 38, Pages 8708-8713Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2853-05.2005
Keywords
nicotine withdrawal; acetylcholine; hippocampus; addiction; learning; tolerance
Categories
Funding
- NIDA NIH HHS [R01 DA017949, R01 DA017949-01A2, T32 DA007237, T32DA07237, DA017949] Funding Source: Medline
- PHS HHS [P5084718] Funding Source: Medline
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The effects of acute nicotine administration (0.09 mg/ kg nicotine), chronic nicotine administration ( 6.3 mg/kg/d nicotine for 14 d), and withdrawal from chronic nicotine administration on fear conditioning in C57BL/6 mice were examined. Mice were trained using two coterminating conditioned stimulus (30s; 85 dB white noise)-unconditioned stimulus (2s; 0.57 mA foot shock) pairings and tested 24 h later for contextual and cued fear conditioning. Acute nicotine administration enhanced contextual fear conditioning, chronic nicotine administration had no effect on contextual fear conditioning, and withdrawal from chronic nicotine administration impaired contextual fear conditioning. Plasma nicotine concentrations were similar after acute and chronic treatment and were within the range reported for smokers. During withdrawal, concentrations of nicotine were undetectable. An acute dose of nicotine ( 0.09 mg/ kg) during withdrawal from chronic nicotine treatment reversed withdrawal-associated deficits in contextual fear conditioning. The results suggest that tolerance to the effects of nicotine on contextual fear conditioning develops with chronic nicotine treatment at a physiologically relevant dose, and withdrawal from this chronic nicotine treatment is associated with impairments in contextual fear conditioning. These findings provide a model of how the effects of nicotine on learning may contribute to the development and maintenance of nicotine addiction.
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