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Motor dysfunction produced by tacrine administration in rats
D L Carriero1, G Outslay, A J Mayorga
1Department of Psychology, University of Connecticut, Storrs 06269-1020, USA.
Pharmacology, Biochemistry, and Behavior
|January 4, 1998
Summary
The anticholinesterase tacrine impairs motor function in rats, causing tremors and reduced activity. These findings in rats align with human studies linking tacrine to Parkinsonian side effects.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Tacrine is an anticholinesterase agent.
- Anticholinesterase agents can have motor side effects.
- Tacrine (Cognex) is used clinically and has reported Parkinsonian side effects.
Purpose of the Study:
- To characterize the motor effects of tacrine in rats.
- To investigate tacrine's impact on locomotion and operant behavior.
- To explore potential mechanisms for tacrine-induced motor impairments.
Main Methods:
- Three experiments were conducted in rats using tacrine at doses of 1.25-5.0 mg/kg.
- Motor effects were assessed through observation of jaw movements, open-field activity, and operant lever pressing.
- Operant behavior analysis included response initiation time and response duration using computerized tracking.
Main Results:
- Tacrine induced dose-dependent tremulous jaw movements and suppressed open-field motor activity.
- Tacrine significantly reduced lever pressing rates in a fixed ratio 5 schedule.
- The primary cause of reduced responding was a substantial increase in response initiation time (pausing), with some increase in response duration at higher doses.
Conclusions:
- Tacrine impairs multiple motor functions in rats, including fine motor control and sustained activity.
- The observed motor deficits, particularly increased pausing, may reflect drug-induced akinesia.
- These findings in rats support the clinical observation of tacrine-induced Parkinsonian side effects and suggest utility for studying these adverse effects.