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The Role of Mitochondrial Biogenesis and Α2-Adrenergic Receptors of the Hippocampal CA1 Region in Morphine-Induced Memory Impairment
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E Beirami *    , SM Seyedhosseini Tamijani |
| 1.Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, I.R.Iran. , elmira.beirami@khu.ac.ir |
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Abstract: (321 Views) |
Background and Objective: Mitochondrial biogenesis and the adrenergic system play an important role in cognitive processes. The dorsal hippocampus (CA1) has a high distribution of α2-adrenergic receptors. Given that morphine can cause memory impairment, the aim of the present study was to investigate the role of mitochondrial biogenesis and α2-adrenergic receptors in the CA1 region in morphine-induced memory impairment.
Methods: This experimental study included four experimental groups: 1) morphine, 2) clonidine and clonidine + morphine, 3) yohimbine and yohimbine + morphine, 4) yohimbine + clonidine + morphine. The total number of animals in these experiments included 208 adult male Wistar rats, which were divided into 26 groups of 8. Intraperitoneal injection of morphine (4, 5, 6 mg/kg) was done to cause memory impairment. Different doses of α2-adrenergic receptor agonists and antagonists (clonidine and yohimbine, respectively) (1, 2, 4 μg/rat) were injected into the CA1 region of the hippocampus. A shuttle box apparatus was used to examine passive avoidance memory, and the ELISA technique was used to measure the expression levels of factors involved in mitochondrial biogenesis (PGC-1α, NRF-1 and TFAM) in the CA1 region. Then, the groups were examined and compared in terms of memory impairment.
Findings: Injection of the effective dose of morphine (6 mg/kg) impaired passive avoidance memory compared to the saline group (118.88±15.62 vs. 285.13±7.50) (p<0.001). Injection of clonidine (4 µg/rat) into the CA1 region increased memory compared to the saline group (291.25±6.86 vs. 230.25±5.64) (p<0.05), and its injection before the effective dose of morphine prevented memory impairment by morphine (250.62±13.72 vs. 96.12±14.57) (p<0.001). Yohimbine injection (4 µg/rat) resulted in a poor memory compared to saline group (161±19.69 vs. 241±15.20) (p<0.05) and its injection before low dose of morphine (4 mg/kg) caused inhibition of memory recall (113.12±13.9 vs. 241.5±21.59) (p<0.001). Low dose yohimbine injection (1 µg/rat) caused inhibition of clonidine-induced response while clonidine plus morphine caused inhibition of memory recall. The effective dose of morphine also decreased the expression levels of PGC-1α (118.25±19.85 vs. 185.1±8.8), NRF-1 (63.42±6 vs. 106.62±11.95) and TFAM (19.5±0.89 vs. 37.6±5.44) in the CA1 region compared to the saline group (p<0.05). Injection of the effective dose of clonidine before morphine increased the expression of these factors (p<0.05), while this increase was inhibited by injection of a low dose of yohimbine.
Conclusion: The results of the study showed that mitochondrial biogenesis and α2-adrenergic receptors in the hippocampal CA1 region may be involved in morphine-induced memory impairment. |
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| Keywords: Mitochondrial Biogenesis, Α2-Adrenergic Receptors, Morphine, Memory Impairment. |
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Full-Text [PDF 638 kb]
(43 Downloads)
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Type of Study: Experimental |
Subject:
Physiology
Received: 2024/05/3 | Accepted: 2024/09/7 | Published: 2025/08/26
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