Age-related differential sensitivity to MK-801-induced locomotion and stereotypy in C57BL/6 mice

• Published in: European journal of pharmacology Vol. 580; no. 1; pp. 161 - 168
• Main Authors: Qi, Chunting, Zou, Hong, Zhang, Ruizhong, Zhao, Guoping, Jin, Meilei, Yu, Lei
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 02.02.2008; Elsevier
• Subjects: Age Factors; Aging; Aging - physiology; Animals; Biological and medical sciences; Differential drug sensitivity; Disease Models, Animal; Dizocilpine maleate; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - pharmacology; Locomotion; Locomotion - drug effects; Male; Medical sciences; Mice; Mice, Inbred C57BL; Noncompetitive NMDA receptor antagonist; Pharmacology. Drug treatments; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Schizophrenia - physiopathology; Stereotyped Behavior - drug effects; Stereotypy; Differential drug sensitivity; Aging; Locomotion; Noncompetitive NMDA receptor antagonist; Dizocilpine maleate; Stereotypy; Drug; Senescence; Dizocilpine; Rodentia; Neuroprotective agent; Glutamate receptor; Vertebrata; Sensitivity; Mammalia; Mouse; Animal; Antagonist; NMDA receptor; Age
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.07.071

Psychomotor effects elicited by systemic administration of the noncompetitive NMDA ( N-methyl- d-aspartate) receptor antagonist MK-801 (dizocilpine maleate) represent perturbation of glutamatergic pathways, providing an animal model for psychotic symptoms of schizophrenia. Hyperlocomotion and stereotypy are the two main psychomotor behaviors induced by MK-801. This study compared MK-801-induced hyperlocomotion and stereotypy in young (1-month old) and aged mice (12-month old), in order to determine how the aging process may influence these behaviors. The tested MK-801 doses ranged from 0.015 to 1 mg/kg. The data indicated that MK-801 impacted the aged mice more pronouncedly than the young mice, as both hyperlocomotion and stereotypy were increased significantly more in the aged mice relative to the young mice. These results suggest an age-related increase in MK-801 sensitivity in mice.