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Gamma-Hydroxybutyrate (GHB) induces cognitive deficits and affects GABAreceptors and IGF-1 receptors in male rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2014 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 269, 164-174 p.Article in journal (Refereed) Published
Abstract [en]

In recent years, the abuse of the club drug Gamma-hydroxy butyric acid (GHB) has become increasingly frequent among adolescents. The drug induces euphoria but can also result in sedation, anaesthesia as well as short-term amnesia. In addition, the abuse of GHB is reported to cause cognitive impairments. The mechanism by which GHB induces impairment in learning and memory has not been fully clarified. The present study investigates the impact on spatial learning and memory using a water maze test in rats treated with GHB. The behavioural data is combined with an autoradiographic analysis of the GABAB and the IGF-1 receptor systems. The results demonstrate that the GHB treated animals display an impaired performance in the water maze test as compared to controls. In addition, significant alterations in GABAB and IGF-1 receptor density as well as GABAB receptor functionality, were observed in several brain regions associated with cognitive functions e.g. hippocampus. To conclude, our findings suggest that GHB treatment can affect spatial learning and memory, and that this outcome at least to some extent is likely to involve both GABAB and IGF-1 receptors.

Place, publisher, year, edition, pages
2014. Vol. 269, 164-174 p.
Keyword [en]
Gamma-hydroxybutyrate (GHB), GABAB and IGF-1 receptors, Autoradiography, GTPgammaS-assay, Rat, Central nervous system (CNS).
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
Identifiers
URN: urn:nbn:se:uu:diva-185421DOI: 10.1016/j.bbr.2014.04.034ISI: 000337866400021OAI: oai:DiVA.org:uu-185421DiVA: diva2:572269
Funder
Swedish Research Council, 9459
Available from: 2012-11-27 Created: 2012-11-23 Last updated: 2017-12-07Bibliographically approved
In thesis
1. The Impact of Growth Hormone and Gamma-Hydroxybutyrate (GHB) on Systems Related to Cognition
Open this publication in new window or tab >>The Impact of Growth Hormone and Gamma-Hydroxybutyrate (GHB) on Systems Related to Cognition
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drug dependence is a serious and increasing problem in our society, especially among adolescents. The use of the large variety of substances available can result in a range of physiological and psychological adverse effects on individuals and negative consequences on the society overall. Several different types of drugs induce neurotoxicological damages, which in turn can generate impairment in for example the reward system and affect cognitive parameters.

 The drug gamma-hydroxybutyrate (GHB) is usually considered a harmless compound among abusers, but has now shown to be highly addictive. Furthermore, GHB can cause memory impairments in both humans and animals. On the contrary, growth hormone (GH) and its main mediator insulin-like growth factor 1 (IGF-1) have recently been suggested to improve memory and learning in several studies. The hormones exhibit certain neuroprotective capabilities and have also previously been demonstrated to reverse opioid induced apoptosis in hippocampal cells. These effects and the fact that GHB is shown to increase GH secretion, which attracted considerable attention among body builders, led us to initiate studies on GHB and its impact on relevant systems in the central nervous system (CNS). Thus, the main purpose of the present investigation was to elucidate some of the underlying mechanisms that could account for the effects exerted by GH and GHB in the CNS.

We found that a) GH affects the density and functionality of GABAB-receptors and opioid receptors in the male rat brain, b) GHB induces cognitive deficits and down-regulates GABAB-receptors, c) GHB treatment creates an imbalance between the endogenous opioids Met-enkaphalin-Arg6Phe7 (MEAP) and dynorphin B and increases the levels of MEAP in regions of the brain that are associated with drug dependence, and d) GHB affects the expression of IGF-1 receptors but not the plasma levels of IGF-1. In conclusion, the present work demonstrates that GH interacts with both opioid and GABAB-receptors in the male rat CNS and that GHB has an impact on brain regions associated with cognition and the development of dependence. These observations may be of relevance in many aspects related to addiction and might be translated into humans.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 74 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 168
Keyword
Growth Hormone, Gamma-Hydroxybutyrate, GABAB, Opioids, Insulin-like growth factor 1, Rats, Central Nervous System, Autoradiography, Radioimmunoassay, ELISA, Water Maze, Open Field
National Category
Pharmaceutical Sciences
Research subject
Biological Research on Drug Dependence
Identifiers
urn:nbn:se:uu:diva-185631 (URN)978-91-554-8552-8 (ISBN)
Public defence
2013-01-18, B21, BMC, Husargatan 3, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2012-12-20 Created: 2012-11-27 Last updated: 2013-02-11Bibliographically approved

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Johansson, JennyGrönbladh, AlfhildHallberg, Mathias

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