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Liver-derived IGF-I regulates exploratory activity in old mice.

Journal article
Authors Johan Svensson
Bo Söderpalm
Klara Sjögren
Jörgen Engel
Claes Ohlsson
Published in American journal of physiology. Endocrinology and metabolism
Volume 289
Issue 3
Pages E466-73
ISSN 0193-1849
Publication year 2005
Published at Institute of Physiology and Pharmacology, Dept of Pharmacology
Institute of Internal Medicine, Dept of Medicine
Institute of Internal Medicine
Pages E466-73
Language en
Keywords Age Factors, Aging, physiology, Animals, Exploratory Behavior, physiology, Female, Growth Hormone, metabolism, Habituation, Psychophysiologic, physiology, Insulin-Like Growth Factor I, genetics, metabolism, Liver, physiology, Male, Maze Learning, physiology, Mice, Mice, Knockout, Motor Activity, physiology, Thyroxine, blood, Triiodothyronine, blood
Subject categories Medical and Health Sciences


Growth hormone (GH) replacement in hypopituitary patients improves well-being and initiative. Experimental studies indicate that these psychic effects may be reflected in enhanced locomotor activity in mice. It is unknown whether these phenomena are mediated directly by GH or by circulating IGF-I. IGF-I production in the liver was inactivated at 6-10 wk of age (LI-IGF-I-/- mice), resulting in an 80-85% reduction of circulating IGF-I, and, secondary to this, increased GH secretion. Using activity boxes on three different occasions during 1 wk, 6-mo-old LI-IGF-I-/- mice had similar activity levels, and 14-mo-old mice had a moderate but significant decrease in activity level, compared with control mice. At 20 mo of age, the LI-IGF-I-/- mice displayed a more prominent decrease in activity level with decreased horizontal activity throughout the test period, and at day 1, there were several signs of an altered habituation process with different time patterns of locomotor activity and horizontal activity compared with the control mice. At days 3 and 5, rearing activity was lower in the 20-mo-old LI-IGF-I-/- mice. Anxiety level was unaffected in all age groups, as measured using the Montgomery's elevated plus-maze. In conclusion, old LI-IGF-I-/- mice displayed a decrease in both horizontal and rearing (exploratory) activity level and an altered habituation process. These results indicate that liver-derived IGF-I mediates at least part of the effects of GH on exploratory activity in mice.

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