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Effects of TCP on spatial memory: comparison with MK-801
1Centre de Recherches du Service de Santé des Armées, Unité de Neurotoxicologie, La Tronche, France.
Pharmacology, Biochemistry, and Behavior
|June 1, 1995
Summary
TCP (N-[1-(2-thienyl)cyclohexyl]piperidine), an NMDA receptor antagonist, does not impair memory at therapeutic doses, unlike MK-801. This suggests TCP may offer seizure protection without cognitive side effects.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- NMDA receptor antagonists, such as phencyclidine (PCP) derivatives, show promise for treating seizures.
- However, NMDA receptor antagonists can negatively impact cognitive functions, particularly spatial learning.
- TCP (N-[1-(2-thienyl)cyclohexyl]piperidine) is a PCP derivative with demonstrated antiepileptic and neuroprotective effects.
Purpose of the Study:
- To investigate the effects of TCP on memory and spatial learning.
- To compare TCP's cognitive effects with MK-801, a well-studied NMDA receptor antagonist.
- To determine if therapeutic doses of TCP cause memory impairment.
Main Methods:
- Rats were administered varying doses of TCP (0.5, 1, 2 mg/kg) or MK-801 (0.05, 0.1, 0.2 mg/kg) daily.
- Cognitive function was assessed using the Morris water maze test.
- Locomotor activity and side effects were also monitored.
Main Results:
- Both TCP and MK-801 impaired spatial learning at their highest doses.
- MK-801 at 0.1 mg/kg impaired spatial memory, while TCP at 1 mg/kg did not.
- TCP exhibited transient locomotor side effects, resolving within 30 minutes post-injection.
Conclusions:
- At its minimal effective antiseizure dose (1 mg/kg), TCP does not induce memory impairment, unlike MK-801.
- TCP presents a potential therapeutic advantage by offering seizure control without significant cognitive deficits.
- TCP's transient locomotor effects further enhance its potential clinical utility.