title: The mRNA expression of insulin-like growth factor-1 (Igf1) is decreased in the rat frontal cortex following gamma-hydroxybutyrate (GHB) administration.
abstract: In recent years, growth hormone (GH), together with its secondary mediators insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2), have been highlighted for their beneficial effects in the central nervous system (CNS), in particular as cognitive enhancers. Cognitive processes, such as learning and memory, are known to be impaired in individuals suffering from substance abuse. In the present study, we investigated the effect of gamma-hydroxybuturate (GHB), an illicit drug used for its sedating and euphoric properties, on genes associated with the somatotrophic axis in regions of the brain important for cognitive function. Sprague Dawley rats (n=36) were divided into three groups and administered either saline, GHB 50mg/kg or GHB 300mg/kg orally for seven days. The levels of Ghr, Igf1 and Igf2 gene transcripts were analyzed using qPCR in brain regions involved in cognition and dependence. The levels of IGF-1 in blood plasma were also determined using ELISA. The results demonstrated a significant down-regulation of Igf1 mRNA expression in the frontal cortex in high-dose treated rats. Moreover, a significant correlation between Igf1 and Ghr mRNA expression was found in the hippocampus, the frontal cortex, and the caudate putamen, indicating local regulation of the GH/IGF-1 axis. To summarize, the current study concludes that chronic GHB treatment influences gene expression of Ghr and Igf1 in brain regions involved in cognitive function.
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden. Electronic address: erika.brolin@farmbio.uu.se.
authors.forename: Erika
authors.initials: E
authors.lastname: Brolin
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Zelleroth
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden; The Beijer Laboratory, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Shanti
authors.initials: S
authors.lastname: Diwakarla
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Fred
authors.initials: F
authors.lastname: Nyberg
authors.affiliation: Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden; The Beijer Laboratory, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Alfhild
authors.initials: A
authors.lastname: Grönbladh
authors.affiliation: The Beijer Laboratory, Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 591, SE-751 24 Uppsala, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hallberg
mesh_terms: D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D012978:Sodium Oxybate / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D012978:Sodium Oxybate; D017526:Receptor, IGF Type 1
keywords: Central nervous system (CNS); Cognition; Frontal cortex (FC); Gamma-hydroxybutyrate (GHB); Growth hormone (GH); Insulin-like growth factor-1 (IGF-1)