Maturation of locomotor and Fos responses to the NMDA antagonists, PCP and MK-801.
Antagonists at the N-methyl-D-aspartate (NMDA)-type glutamate receptor, such as phencyclidine (PCP) and dizocilpine (MK-801), are well-known to evoke increases in locomotor activity in adult rats and mice. However, little is known about the effects of NMDA antagonists on locomotor activity as a function of development. The present study examined locomotor responses to PCP or MK-801 in male rats of varying ages and found that prepubertal rats were more sensitive to the locomotor-elevating effects of PCP (1.5 mg/kg and 3. 0 mg/kg, s.c.) than were adults. Locomotor responses to MK-801 (0.1 and 0.2 mg/kg, s.c.) were not dependent on age. The age-dependent response to PCP may be related to developmental events in the motor cortex, since more Fos-immunoreactive neurons were observed in the motor cortex of prepubertal animals after PCP administration relative to adult animals. An opposite pattern of age-dependent Fos responses was observed in the posterior retrosplenial cortex. The results suggest that locomotor responses to NMDA antagonists can be influenced in an age- and drug-dependent manner and that maturational events in the motor cortex may modify responses to PCP.
Department of Psychiatry, Campus Box 8134, Washington University School of Medicine, St. Louis, MO 63110, USA.
P S
PS
Jacobs
B M
BM
Taylor
M E
ME
Bardgett
D000367:Age Factors; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D017781:Genes, Immediate-Early / Q000502:physiology; D006179:Gyrus Cinguli / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009044:Motor Cortex / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D010622:Phencyclidine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012741:Sexual Maturation / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D010622:Phencyclidine