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.
Jacobs
P S
PS
Department of Psychiatry, Campus Box 8134, Washington University School of Medicine, St. Louis, MO 63110, USA.
Taylor
B M
BM
Bardgett
M E
ME
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