Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory

The age-related decline in growth hormone is one of the most robust endocrine markers of biological aging and has been hypothesized to contribute to the physiological deficits observed in aged animals. However, there have been few studies of the impact of this hormonal decline on brain aging. In this study, the effect of long-term subcutaneous administration of [D-Ala2]-growth hormone-releasing hormone (GHRH) on one measure of brain function, memory, was investigated. Animals were injected daily with 2.3 microg of [D-Ala2]-GHRH or saline from 9 to 30 months of age, and the spatial learning and reference memory of animals were assessed by using the Morris water maze and compared with those of 6-month-old animals. Results indicated that spatial memory decreased with age and that chronic [D-Ala2]-GHRH prevented this age-related decrement (24% improvement in the annulus-40 time and 23% improvement in the number of platform crossings compared with saline treated, age-matched controls; p < .05 each). No changes were noted in sensorimotor performance. [D-Ala2]-GHRH attenuated the age-related decline in plasma concentrations of insulinlike growth factor-1 (IGF-1) (p <.05). These data suggest that growth hormone and IGF-1 have important effects on brain function, that the decline in growth hormone and IGF-1 with age contributes to impairments in reference memory, and that these changes can be reversed by the chronic administration of GHRH.