Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats

Abstract

Changes in locomotor and stereotypic activities induced by an i.p. injection of either (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cycloheptan-5,10- imine maleate (dizocilpine or MK-801; 0.3 mg/kg) or D-amphetamine sulfate (AMPH; 1.5 mg/kg) were studied in male Mill Hill hooded rats of different age. The following age groups of animals were considered: 28-30 postnatal day (PND)-old rats (peripubertal), 48-50 PND-old (pubertal), 3-month-old (adults), 12-month-old (middle-aged) and 24-month-old (aged). The motor response was measured by an automated animal activity measuring system. The obtained results showed that: (1) in contrast to AMPH, MK-801 induced more pronounced increases of both locomotor and stereotypic activities in peripubertal and pubertal than in adult and aged rats; (2) AMPH induced the same locomotor and stereotypic activity increase in pubertal, adult and middle-aged rats; (3) both AMPH and MK-801 led to a senescence-related decrease of motor activity. These data suggest that the balance of the glutamatergic and dopaminergic systems changes during aging. Such a change is important in understanding schizophrenia and the motor system decline observed in the later stages of life.