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The effects of nicotine on locomotor activity in non‐tolerant and tolerant rats
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1--Rats were tested for locomotor activity in photocell cages, for 80 min starting immediately after subcutaneous injection of (-)-nicotine bitartrate or 0.9% w/v NaCl solution (saline). In non-tolerant subjects, nicotine (0.1 to 0.4 mg/kg base) depressed activity and induced ataxia in the first 20 min, but increased activity later in the session; these actions were dose-dependent. 2--Tolerance was studied by comparing rats given nicotine (0.4 mg/kg s.c.) every day with control rats given saline instead. Each week, every subject was tested once with nicotine (0.4 mg/kg) and once with saline. With daily or even weekly injections of nicotine, the initial depressant action of the drug was replaced by a dose-dependent stimulant action which occurred throughout the session. In these tolerant animals, little ataxia was seen except when a larger dose of 0.8 mg/kg was given. Tolerance to the depressant action of nicotine persisted for at least 3 weeks. 3--In non-tolerant subjects, mecamylamine (0.5, 1.0 mg/kg s.c.) prevented the initial depressant action of nicotine (0.4 mg/kg). In tolerant rats, the locomotor stimulant action of nicotine (0.4 mg/kg) was prevented by mecamylamine (0.1, 0.32, 1.0 mg/kg s.c.) in a dose-related way; the quaternary ganglion blocker, hexamethonium (0.2, 1.0, 5.0 mg/kg s.c.) had little or no such effect. Neither mecamylamine nor hexamethonium altered activity when given alone. 4--It is suggested that a few treatments with nicotine can unmask a stimulant action of the drug, probably of central origin, which possibly reflects a stimulation of nicotine receptors.
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“For nicotine, animal studies have shown that repeated intermittent injections of nicotine typically cause sensitization or enhancement of the drug’s locomotor activating effects (L. K. Baker et al., 2013; Benwell & Balfour, 1992; Clarke & Kumar, 1983; Vezina, McGehee, & Green, 2007).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Clarke & Kumar, 1983
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Metadata
- Authors
- Clarke, P. B. S., & Kumar, R.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1983-02
- Volume
- 78
- Issue
- 2
- Pages
- 329-337
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2044704
- OpenAlex
- W2054668681
- Cited by
- 457
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 7 · 2021: 1 · 2020: 5 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 11 · 2014: 8 · 2013: 7 · 2012: 12
- FWCI
- 4.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, locomotor activity, nicotine tolerance, mecamylamine, hexamethonium, nicotinic acetylcholine receptors, dose-dependent effects
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Drug Tolerance, Hexamethonium Compounds, Humans, Male, Mecamylamine, Motor Activity, Nicotine, Substance Withdrawal Syndrome, Hexamethonium, Rats
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