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Effect of Pretreatment With Intracerebroventricular Injection of Minocycline on Morphine-Induced Memory Impairment in Passive Avoidance Test: Role of P-Creb and C-Fos Expression in the Dorsal Hippocampus and Basolateral Amygdala Regions Publisher Pubmed



Hamidkhaniha S1 ; Bashiri H2 ; Omidi A3 ; Hosseinichegeni A4 ; Tavangar SM5 ; Sabouri S6 ; Montazeri H7 ; Sahebgharani M1
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  3. 3. Department of Anatomical Sciences, Medical Sciences Faculty, Tarbiat Modares University, Tehran, Iran
  4. 4. Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran
  5. 5. Department of Pathology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
  7. 7. School of Pharmacy- International Campus, Iran University of Medical Sciences, Tehran, Iran

Source: Clinical and Experimental Pharmacology and Physiology Published:2019


Abstract

Minocycline as a member of the tetracycline family is a lipophilic broad-spectrum antibiotic, which can display some non-antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine-induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho-cAMP response element-binding protein (P-CREB) and c-Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose-dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 μg/rat) prevented morphine-induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P-CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P-CREB in both brain areas. Moreover, there was no significant change in the expression of c-Fos positive cells in above-mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine-induced memory impairment and increased P-CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property. © 2019 John Wiley & Sons Australia, Ltd
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