Modulation of behaviour on trials 1 and 2 in the elevated plus-maze test of anxiety after systemic and hippocampal administration of nicotine
Abstract
Rationale The elevated plus-maze provides a test situation in which distinctive states of anxiety are elicited on trials 1 and 2 and the dorsal hippocampus has previously been shown to mediate the anxiogenic effects of (-)-nicotine in the social interaction test.Objective To determine the effects of a wide dose range of (-)-nicotine on trial 1 and 2 in the plus-maze after systemic administration and whether the dorsal hippocampus is a site mediating the anxiogenic effect of nicotine.Methods (-)-Nicotine (0.001, 0.005, 0.01, 0.05, 0.1, 0.5 and 1 mg/kg) was injected IP 30 min before testing for 5 min in the plus-maze. Rats receiving dorsal hippocampal infusions received bilateral infusions of 0.5 microl of artificial CSF or (-)-nicotine (0.1, 1, 4 or 8 microg). The needle was left in place for 50 s after injection and testing took place 3 min later. Rats tested on trial 1 were naive to the plus-maze, those tested on trial 2 had received a previous 5-min undrugged exposure to the maze 48 h earlier.Results Low doses of (-)-nicotine (0.001, 0.005, 0.01, 0.05 and 0.1 mg/kg, IP) were without effect on either trial, but higher doses (0.5 and 1 mg/kg, IP) had anxiogenic effects on both trials, as shown by decreases in percentage time spent and percentage entries onto the open arms. Infusion of (-)-nicotine (0.1, 1, 4 and 8 microg) bilaterally into the dorsal hippocampus was without effect on trial 1, but 1 microg had an anxiolytic effect on trial 2, shown by an increased percentage time spent on the open arms.Conclusions The results on both trials in the plus-maze after systemic administration of nicotine add to previous reports from the social interaction test that high doses of nicotine have anxiogenic effects. However, the effects of nicotine in the dorsal hippocampus are different in all three anxiety tests (anxiogenic in social interaction, ineffective on trial 1, anxiolytic on trial 2) showing that nicotinic cholinergic control in this brain region may vary depending on the state and/or type of anxiety generated by the test. The brain region(s) underlying the anxiogenic effects of IP nicotine on both trials in the plus-maze remain to be identified.
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Studies finding anxiogenic effects of nicotine used male hooded Lister rats, whereas studies showing anxiolytic effects used male Wistar rats or CD1 mice.
“both Irvine et al. (1999, 2001) and Ouagazzal et al. (1999) studies, which found that nicotine has an anxiogenic effect, used male hooded Lister rats, whereas other studies showing anxiolytic effects of nicotine (Ericson et al., 2000; O’Neill & Brioni, 1994) used male Wistar rats or CD1 mice.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Ouagazzal et al. (1999)
Higher doses of acute nicotine at 0.5 and 1 mg/kg administered intraperitoneally produced increased anxiety in the elevated plus maze.
“Ouagazzal et al. (1999) showed that higher doses of acute nicotine (0.5 and 1 mg/kg) administered intraperitoneally (i.p.) also produced increased anxiety in the EPM.”
From Nicotine addiction and psychiatric disorders (2015) · cites this paper as Ouagazzal et al. (1999)
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- Authors
- Ouagazzal, A.-M., Kenny, P. J., & File, S. E.
- Affiliations
- King's College London (GB)
- Venue
- Psychopharmacology
- Published
- 1999-05-12
- Volume
- 144
- Issue
- 1
- Pages
- 54-60
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2045584395
- Cited by
- 121
- References
- 44
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 6 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 3
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotine, anxiogenic effects, anxiolytic effects, elevated plus maze, dorsal hippocampus, dose-dependent effects, rats, open arm exploration, social interaction test, nicotine dependence, tobacco dependence treatment
- MeSH terms
- Analysis of Variance, Animals, Anxiety, Behavior, Animal, Dose-Response Relationship, Drug, Hippocampus, Male, Nicotine, Maze Learning, Rats
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