DOPAMINE D2 RECEPTOR MECHANISMS CONTRIBUTE TO AGE-RELATED COGNITIVE DECLINE - THE EFFECTS OF QUINPIROLE ON MEMORY AND MOTOR-PERFORMANCE IN MONKEYS

The D2 dopamine (DA) receptor agonist, quinpirole, was characterized in young adult monkeys, young reserpine-treated monkeys and aged monkeys to assess the contribution of DA to age-related loss of prefrontal cortical (PFC) cognitive function, Monkeys were tested on a delayed response memory task that depends on the PFC, and a fine motor task that taps the functions of the motor cortex, In young adult monkeys, low quinpirole doses impaired performance of the PFC and fine motor tasks, while higher doses improved memory performance and induced dyskinesias and ''hallucinatory-like'' behaviors. The pattern of the quinpirole response in reserpine-treated monkeys suggested that the impairments in delayed response and fine motor performance resulted from drug actions at D2 autoreceptors, while the improvement in delayed response performance, dyskinesias and ''hallucinatory-like'' behaviors resulted from actions at postsynaptic receptors. In aged monkeys, low doses of quinpirole continued to impair fine motor performance, but lost their ability to impair delayed response performance. The magnitude of cognitive improvement and the incidence of ''hallucinatory-like'' behaviors were also reduced in the aged animals, suggesting some loss of postsynaptic D2 receptor function, The pattern of results is consistent with the greater loss of DA from the PFC than from motor areas in aged monkey brain (Goldman-Rakic and Brown, 1981; Wenk et al., 1989), and indicates that DA depletion contributes significantly to age-related cognitive decline.

Impairments in embryonic genome activation in rhesus monkey somatic cell nuclear transfer embryos

Somatic cell nuclear transfer (SCNT) is a remarkable process in which a somatic cell nucleus is acted upon by the ooplasm via mechanisms that today remain unknown. Here we show the developmental competence (% blastocyst) of embryos derived from SCNT (21%)

Lead exposure through gestation-only caused long-term learning/memory deficits in young adult offspring

Numerous observations in clinical and preclinical studies indicate that the developing brain is particular sensitive to lead (Pb)'s pernicious effects. However, the effect of gestation-only Pb exposure on cognitive functions at maturation has not been studied. We investigated the potential effects of three levels of Pb exposure (low, middle, and high Pb: 0.03%, 0.09%, and 0.27% of lead acetate-containing diets) at the gestational period on the spatial memory of young adult offspring by Morris water maze spatial learning and fixed location/visible platform tasks. Our results revealed that three levels of Pb exposure significantly impaired memory retrieval in male offspring, but only female offspring at low levels of Pb exposure showed impairment of memory retrieval. These impairments were not due to the gross disturbances in motor performance and in vision because these animals performed the fixed location/visible platform task as well as controls, indicating that the specific aspects of spatial learning/memory were impaired. These results suggest that exposure to Pb during the gestational period is sufficient to cause long-term learning/memory deficits in young adult offspring. (C) 2003 Elsevier Inc. All rights reserved.