Nicotine Tolerance Development
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
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Equipment1
Not specified • Not specified • Not specified • Not specified
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Protocol Steps
Non-tolerant subject testing with nicotine
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
View evidence from paper
“Rats were tested for locomotor activity in photocell cages, for 80 min starting immediately after subcutaneous injection of (-)-nicotine bitartrate”
Tolerance development protocol - daily nicotine treatment
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
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”
Weekly testing of tolerant rats
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
View evidence from paper
“Each week, every subject was tested once with nicotine (0.4 mg/kg) and once with saline”
Testing tolerance persistence
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
View evidence from paper
“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”
Mecamylamine antagonism testing in non-tolerant rats
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
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 testing in tolerant rats
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
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 antagonism testing in tolerant rats
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
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 testing with antagonists alone
Neither mecamylamine nor hexamethonium were given alone to test for independent effects on activity
Note: Neither mecamylamine nor hexamethonium altered activity when given alone
View evidence from paper
“Neither mecamylamine nor hexamethonium altered activity when given alone”