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Chronic administration of morphine using mini-osmotic pumps affects spatial memory in the male rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Division of Biological Research on Drug Dependence)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Division of Biological Research on Drug Dependence)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (Division of Biological Research on Drug Dependence)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. (The Beijer Laboratory)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The use of opioid analgesics to treat non-cancer pain has increased over the years.  Many chronic pain patients suffer from numerous adverse effects, such as reduced quality of life, development of dependence, and cognitive impairments. Cognitive processes are regulated by several systems, one of which involves growth hormone (GH) and its secondary mediator insulin-like growth factor-1 (IGF-1), but also receptors such as the N-methyl-D-aspartate (NMDA)-receptor complex. In the laboratory, repeated injections are commonly used to establish animal models of long-term or chronic drug exposure. However, in the present study, we aimed to mimic a more human dose regimen using constant drug delivery provided by mini-osmotic pumps implanted subcutaneously in male Sprague Dawley rats. After developing opioid tolerance the cognitive function of rats was studied. Spatial learning and memory were evaluated using the Morris water maze (MWM). Moreover, gene expression related to the GH/IGF-1-axis and the NMDA-receptor system were analyzed using quantitative PCR (qPCR) and the levels of IGF-1 in plasma were examined with ELISA. Our results demonstrate that rats exposed to morphine for 27 days display memory impairments in the MWM probe trial. However, the behavioral effects of chronic morphine treatment were not accompanied by any significant differences in terms of mRNA expression or IGF-1 plasma concentration. The animal model used in this study provides a simple and suitable way to investigate the behavioral and neurochemical effects of chronic opioid treatment similar to the exposure seen in human pain patients.

Keyword [en]
Morphine, Morris water maze, mini-osmotic pumps, memory, insulin-like growth factor-1, N-metyl-D-aspartate
National Category
Pharmaceutical Sciences
Research subject
Pharmaceutical Science
Identifiers
URN: urn:nbn:se:uu:diva-317302OAI: oai:DiVA.org:uu-317302DiVA: diva2:1081109
Funder
Swedish Research Council, 9459Forte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2017-03-13 Created: 2017-03-13 Last updated: 2017-03-15
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Brolin, ErikaZelleroth, SofiaHallberg, MathiasGrönbladh, AlfhildNyberg, Fred
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