Insulin-like growth factor I expression alters acute sensitivity and tolerance to ethanol in transgenic mice.
We compared some biobehavioral effects of ethanol in transgenic mice that overexpress insulin-like growth factor I (IGF-I) in brain and in those that exhibit ectopic: brain expression of IGF binding protein I with those in non-transgenic littermate controls. Ethanol-induced sleep in IGF-I transgenic mice was significantly shorter, and in IGF binding protein 1 transgenic mice significantly longer, than in controls. A similar tendency, though not significant, was observed for ethanol-induced hypothermia. The groups did not differ in the degree of ethanol-induced ataxia. IGF-I transgenic mice did not acquire tolerance to either the hypothermic or hypnotic effects of ethanol following 7-day ethanol treatment. In contrast, tolerance in IGF binding protein 1 transgenic mice was significantly more pronounced than in controls. There were no significant differences among the three groups in the peak blood alcohol concentrations or the overall blood alcohol curves following acute ethanol challenge. In general, these data support the prediction made that chronically elevated exposure to IGF-I in IGF-I transgenic mice renders them less susceptible to the effects of ethanol than their non-transgenic siblings, and that overexpression of IGF binding protein 1 has the opposite effect.
Pucilowski
O
O
Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7220, USA.
Ayensu
W K
WK
D'Ercole
A J
AJ
D000818:Animals; D001259:Ataxia / Q000139:chemically induced; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D004361:Drug Tolerance; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D015870:Gene Expression; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012890:Sleep / Q000187:drug effects
D018970:Insulin-Like Growth Factor Binding Protein 1; D000431:Ethanol; D007334:Insulin-Like Growth Factor I