Source Paper
The effects of nicotine on locomotor activity in non‐tolerant and tolerant rats
P.B.S. Clarke, R. Kumar
British Journal of Pharmacology • 1983
Source Paper
P.B.S. Clarke, R. Kumar
British Journal of Pharmacology • 1983
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.
Objective: Assessment of tolerance development to nicotine's effects by comparing daily or weekly nicotine-treated rats with saline control rats in locomotor activity tests
This is a Nicotine Tolerance Development protocol using rat as the model organism. The procedure involves 8 procedural steps, 1 equipment items, 4 materials. Extracted from a 1983 paper published in British Journal of Pharmacology.
Model and subjects
rat • Not specified • unknown • Not specified • Not specified
Study window
~3 week study window | ~10.7 hours hands-on
Core workflow
Non-tolerant subject testing with nicotine • Tolerance development protocol - daily nicotine treatment • Weekly testing of tolerant rats
Primary readouts
Key equipment and reagents
Verified items
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Rats were placed in photocell cages and tested for locomotor activity for 80 minutes starting immediately after subcutaneous injection of (-)-nicotine bitartrate at doses of 0.1 to 0.4 mg/kg base
Note: Nicotine depressed activity and induced ataxia in the first 20 minutes, but increased activity later in the session; actions were dose-dependent
“Rats were tested for locomotor activity in photocell cages, for 80 min starting immediately after subcutaneous injection of (-)-nicotine bitartrate”
Rats were given nicotine (0.4 mg/kg s.c.) every day to develop tolerance, while control rats received saline injections instead
Note: Tolerance was studied by comparing daily nicotine-treated rats with saline control rats
“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 in photocell cages for 80 minutes
Note: With daily or even weekly injections of nicotine, the initial depressant action was replaced by dose-dependent stimulant action throughout the session
“Each week, every subject was tested once with nicotine (0.4 mg/kg) and once with saline”
Tolerant rats were tested with a larger dose of nicotine (0.8 mg/kg) to assess tolerance persistence
Note: Little ataxia was seen in tolerant animals except when the larger dose of 0.8 mg/kg was given. Tolerance to the depressant action persisted for at least 3 weeks
“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”
Non-tolerant rats received mecamylamine (0.5, 1.0 mg/kg s.c.) followed by nicotine (0.4 mg/kg) to test prevention of initial depressant action
Note: Mecamylamine prevented the initial depressant action of nicotine in non-tolerant subjects
“In non-tolerant subjects, mecamylamine (0.5, 1.0 mg/kg s.c.) prevented the initial depressant action of nicotine (0.4 mg/kg)”
Tolerant rats received mecamylamine (0.1, 0.32, 1.0 mg/kg s.c.) followed by nicotine (0.4 mg/kg) to test dose-related prevention of stimulant action
Note: The locomotor stimulant action of nicotine was prevented by mecamylamine in a dose-related way
“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”
Tolerant rats received hexamethonium (0.2, 1.0, 5.0 mg/kg s.c.) followed by nicotine (0.4 mg/kg) to test ganglion blocker effects
Note: Hexamethonium had little or no effect on preventing the stimulant action of nicotine in tolerant rats
“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 were given alone to test for independent effects on activity
Note: Neither mecamylamine nor hexamethonium altered activity when given alone
“Neither mecamylamine nor hexamethonium altered activity when given alone”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
Assessment of tolerance development to nicotine's effects by comparing daily or weekly nicotine-treated rats with saline control rats in locomotor activity tests
Objective
Assessment of tolerance development to nicotine's effects by comparing daily or weekly nicotine-treated rats with saline control rats in locomotor activity tests
Subjects
From paperrat • Not specified • unknown • Not specified • Not specified
Cohort notes
From paperRats were divided into non-tolerant and tolerant groups based on treatment history
Non-tolerant subject testing with nicotine (80 minutes)
Tolerance development protocol - daily nicotine treatment (Daily injections over multiple weeks)
Weekly testing of tolerant rats (80 minutes per test; weekly testing schedule)
Testing tolerance persistence (80 minutes)
Locomotor activity measured in photocell cages
From paperNot specified
Artifact type
Longitudinal gait metrics and per-animal performance tables
Comparison focus
Compare recovery trajectory across post-injury timepoints and treatment conditions
Presence and severity of ataxia
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Initial depressant action of nicotine (first 20 minutes)
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Later stimulant action of nicotine
From paperNot specified
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Locomotor activity measured in photocell cages
From paperRaw artifact
Per-run gait capture with paw placement, timing, and stride features for each animal
Processed artifact
Cleaned gait metrics table and recovery trend summary across timepoints
Final reported form
Group comparisons of gait indices, stride metrics, or recovery curves
Presence and severity of ataxia
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Initial depressant action of nicotine (first 20 minutes)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Later stimulant action of nicotine
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not specified
Scoring or quantification
Quantify the primary readouts for this experiment: Locomotor activity measured in photocell cages; Presence and severity of ataxia; Initial depressant action of nicotine (first 20 minutes); Later stimulant action of nicotine.
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Locomotor activity measured in photocell cages, Presence and severity of ataxia, Initial depressant action of nicotine (first 20 minutes), Later stimulant action of nicotine.
Source links and direct wording from the methods section for validation and deeper review.
Citation
P.B.S. Clarke et al. (1983). The effects of nicotine on locomotor activity in non‐tolerant and tolerant rats. British Journal of Pharmacology
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