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L-beta-methylamino-alanine-induced behavioral changes in rats
Y Matsuoka1, Z Rakonczay, E Giacobini
1Department of Pharmacology, Neurology, Southern Illinois University School of Medicine, Springfield 62794-9230.
Pharmacology, Biochemistry, and Behavior
|March 1, 1993
Summary
Infusing L-beta-N-methylamino-L-alanine (L-BMAA) into rat brains caused seizures and rigidity. Non-NMDA receptor antagonist DNQX reduced seizure severity, suggesting L-BMAA affects multiple excitatory amino acid receptors.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- L-beta-N-methylamino-L-alanine (L-BMAA) is a non-protein amino acid with potential neurotoxic effects.
- Excitatory amino acid receptors play crucial roles in neuronal function and excitotoxicity.
Purpose of the Study:
- To investigate the neurobehavioral effects of L-BMAA in rats.
- To determine the involvement of NMDA and non-NMDA glutamate receptors in L-BMAA-induced neurotoxicity.
Main Methods:
- Stereotactic infusion of L-BMAA (500 micrograms) into the lateral ventricle of rats.
- Behavioral observation for signs of neurotoxicity (splay, convulsions, rigidity, grooming, facial tremor).
- Electroencephalograph (EEG) recording to assess epileptiform discharges.
- Administration of glutamate receptor antagonists (DNQX, AP-5, MK-801) to evaluate their effects on L-BMAA-induced behaviors.
Main Results:
- L-BMAA infusion induced splay, clonic convulsions, and rigidity in approximately 60% of rats, accompanied by epileptiform EEG discharges.
- DNQX significantly reduced the duration and severity of L-BMAA-induced clonic convulsions.
- AP-5 and MK-801 did not reduce convulsion severity but prolonged the latency of L-BMAA-induced clonic convulsions.
- MK-801 abolished L-BMAA-induced rigidity, while DNQX and AP-5 partially inhibited it.
- L-BMAA-induced splay was unaffected by DNQX and AP-5 but slightly enhanced by MK-801.
- Various L-BMAA-induced behaviors were modulated by DNQX, AP-5, and MK-801.
Conclusions:
- L-BMAA elicits significant neurobehavioral alterations in rats, including seizure-like activity and motor disturbances.
- The findings indicate that L-BMAA-induced neurotoxicity involves the activation of multiple excitatory amino acid receptor subtypes.
- Non-NMDA glutamate receptors appear to play a significant role in mediating the convulsive effects of L-BMAA, while both NMDA and non-NMDA receptors are implicated in other behavioral changes.