Tolerance to nicotine's effects in the elevated plus-maze and increased anxiety during withdrawal
Abstract
In the elevated plus-maze test of anxiety, nicotine (0.1 mg/kg sc; 30 min after injection) had a significant anxiogenic effect, shown by specific decreases in the percentage of time spent on the open arms and in the percentage of open-arm entries. Tolerance developed to this anxiogenic effect after 7 days of nicotine treatment (0.1 mg/kg/day). Five minutes after an acute injection, nicotine (0.1 mg/kg) was ineffective, but after 7 days of treatment a significant anxiolytic effect, shown by specific increases in the percentage of time spent on the open arms and in the percentage of open-arm entries, emerged. After 14 days of nicotine treatment, tolerance developed to this anxiolytic effect. There was a complete dissociation between the effects of nicotine on the measures of anxiety, and on the locomotor activity as measured by closed-arm entries. No changes in closed-arm entries were found after acute administration of nicotine, but rats tested 30 min after their 7th injection made significantly fewer, and those tested 5 min after their 14th injection made significantly more, entries than their respective controls. Rats that were tested after 24 h withdrawal from six daily nicotine injections showed a significant anxiogenic effect. A low dose of nicotine (5 ng) injected into the dorsal hippocampus was without effect in vehicle pretreated rats, but it was able to reverse the anxiogenic effect found after 24 h of withdrawal from 6 days of nicotine treatment.
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Subcutaneous acute nicotine at 0.1 mg/kg increased anxiety-like behavior in the elevated plus maze 30 minutes after injection.
“Irvine et al. (2001) found that subcutaneous injections of acute nicotine (0.1 mg/kg) increased anxiety-like behavior in the EPM 30 min after injection.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Irvine et al. (2001)
Nicotine injections 5 minutes before the elevated plus maze test had an anxiolytic effect after 7 days of repeated administration.
“Irvine et al. (2001) also found that injections 5 min before the EPM test had an anxiolytic effect after 7 days of repeated administration.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Irvine et al. (2001)
Rats tested 24 hours after the last nicotine injection showed increased anxiety during withdrawal, and this effect was reversed by dorsal hippocampal infusions of nicotine.
“rats tested 24 h after the last nicotine injection showed increased anxiety during withdrawal and this effect was reversed by dorsal hippocampal infusions of nicotine (Irvine et al., 2001).”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Irvine et al., 2001
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- Authors
- Irvine, E. E., Cheeta, S., & File, S. E.
- Affiliations
- King's College London (GB)
- Corresponding author
- File, Sandra E
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 68
- Issue
- 2
- Pages
- 319-325
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2094626870
- Cited by
- 88
- References
- 55
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, tolerance (pharmacology and immunology), nicotine withdrawal, anxiety, anxiogenic effects, anxiolytic effects, locomotor activity, dorsal hippocampus, elevated plus maze, rats
- MeSH terms
- Animals, Anxiety, Drug Tolerance, Hippocampus, Male, Motor Activity, Nicotine, Substance Withdrawal Syndrome, Nicotinic Agonists, Rats
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