Mecamylamine Antagonism Test
Objective: Evaluation of mecamylamine's ability to block nicotine-induced locomotor effects in both non-tolerant and tolerant rats
This is a Mecamylamine Antagonism Test protocol using rat as the model organism. The procedure involves 6 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 baseline testing • Tolerance induction • Mecamylamine antagonism test in non-tolerant subjects
Primary readouts
- Locomotor activity measured via photocell detection
- Presence and severity of ataxia
- Initial depressant action of nicotine (first 20 minutes)
- Later stimulant action of nicotine
Key equipment and reagents
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Protocol Steps
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Non-tolerant subject baseline testing
Rats were tested for locomotor activity in photocell cages for 80 minutes starting immediately after subcutaneous injection of nicotine (0.1 to 0.4 mg/kg base) or saline
Note: Nicotine depressed activity and induced ataxia in first 20 minutes, then increased activity later; actions were dose-dependent
View evidence from paper
“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)”
Tolerance induction
Rats were given daily or weekly injections of nicotine (0.4 mg/kg s.c.) while control rats received saline instead. Each week, every subject was tested once with nicotine (0.4 mg/kg) and once with saline
Note: With daily or weekly nicotine injections, initial depressant action was replaced by dose-dependent stimulant action throughout session. Little ataxia seen except at 0.8 mg/kg dose
View evidence from paper
“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”
Mecamylamine antagonism test in non-tolerant subjects
Non-tolerant rats received subcutaneous injection of mecamylamine (0.5, 1.0 mg/kg) followed by nicotine (0.4 mg/kg) and were tested for locomotor activity in photocell cages for 80 minutes
Note: Mecamylamine prevented the initial depressant action of nicotine in non-tolerant subjects
View evidence from paper
“In non-tolerant subjects, mecamylamine (0.5, 1.0 mg/kg s.c.) prevented the initial depressant action of nicotine (0.4 mg/kg)”
Mecamylamine antagonism test in tolerant subjects
Tolerant rats received subcutaneous injection of mecamylamine (0.1, 0.32, 1.0 mg/kg) followed by nicotine (0.4 mg/kg) and were tested for locomotor activity in photocell cages for 80 minutes
Note: Mecamylamine prevented the locomotor stimulant action of nicotine in a dose-related manner
View evidence from paper
“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”
Hexamethonium comparison test in tolerant subjects
Tolerant rats received subcutaneous injection of hexamethonium (0.2, 1.0, 5.0 mg/kg) followed by nicotine (0.4 mg/kg) and were tested for locomotor activity in photocell cages for 80 minutes
Note: Hexamethonium had little or no effect on blocking nicotine-induced locomotor stimulation in tolerant rats
View evidence from paper
“the quaternary ganglion blocker, hexamethonium (0.2, 1.0, 5.0 mg/kg s.c.) had little or no such effect”
Control tests for antagonists alone
Mecamylamine and hexamethonium were tested alone (without nicotine) to assess their effects on baseline locomotor activity
Note: Neither mecamylamine nor hexamethonium altered activity when given alone
View evidence from paper
“Neither mecamylamine nor hexamethonium altered activity when given alone”