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This Article Full Text Full Text (PDF) All Versions of this Article: 289/3/E466    most recent 00425.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Svensson, J. Articles by Ohlsson, C. Search for Related Content PubMed PubMed Citation Articles by Svensson, J. Articles by Ohlsson, C.

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

¹Research Centre for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska University Hospital; and ²Department of Pharmacology, Göteborg University, Göteborg, Sweden

Submitted 16 September 2004 ; accepted in final form 18 April 2005

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.

circulating insulin-like growth factor I; activity box; locomotor activity; rearing activity; habituation