SB-334867 (an Orexin-1 Receptor Antagonist) Effects on Morphine-Induced Sensitization in Mice—a View on Receptor Mechanisms
Autor: | Piotr Listos, Małgorzata Łupina, Jolanta Kotlinska, Izabela Gutowska, Joanna Listos, Sylwia Talarek, Maciej Tarnowski, Irena Baranowska-Bosiacka |
---|---|
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Receptor Adenosine A2A medicine.drug_class Neuroscience (miscellaneous) Motor Activity Pharmacology Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine SB-334867 Opioid addiction Orexin Receptors Dopamine medicine Animals Urea RNA Messenger Naphthyridines Adenosine receptor expression Sensitization Benzoxazoles Iba-1 Morphine GFAP Receptor Adenosine A1 business.industry Brain Receptor antagonist Adenosine Adenosine receptor Orexin 030104 developmental biology medicine.anatomical_structure nervous system Neurology Astrocytes Orexin Receptor Antagonists Dopamine receptor expression Microglia business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Molecular Neurobiology |
ISSN: | 1559-1182 0893-7648 |
Popis: | The present study focused upon the role of SB-334867, an orexin-1 receptor antagonist, in the acquisition of morphine-induced sensitization to locomotor activity in mice. Behavioral sensitization is an enhanced systemic reaction to the same dose of an addictive substance, which assumingly increases both the desire for the drug and the risk of relapse to addiction. Morphine-induced sensitization in mice was achieved by sporadic doses (five injections every 3 days) of morphine (10 mg/kg, i.p.), while a challenge dose of morphine (10 mg/kg) was injected 7 days later. In order to assess the impact of orexin system blockade on the acquisition of sensitization, SB-334867 was administered before each morphine injection, except the morphine challenge dose. The locomotor activity test was performed on each day of morphine administration. Brain structures (striatum, hippocampus, and prefrontal cortex) were collected after behavioral tests for molecular experiments in which mRNA expression of orexin, dopamine, and adenosine receptors was explored by the qRT-PCR technique. Additionally, the mRNA expression of markers, such as GFAP and Iba-1, was also analyzed by the same technique. SB-334867 inhibited the acquisition of morphine-induced sensitization to locomotor activity of mice. Significant alterations were observed in mRNA expression of orexin, dopamine, and adenosine receptors and in the expression of GFAP and Iba-1, showing a broad range of interactions in the mesolimbic system among orexin, dopamine, adenosine, and glial cells during behavioral sensitization. Summing up, the orexin system may be an effective measure to inhibit morphine-induced behavioral sensitization. |
Databáze: | OpenAIRE |
Externí odkaz: |