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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: (70 Views) |
Background and Objective: Mitochondrial biogenesis and adrenergic system are important in cognitive processes. Dorsal hippocampus (CA1) has abundant distribution of α2-adrenergic receptors. Considering that morphine can cause memory impairment, the aim of study was to investigate the role of mitochondrial biogenesis and α2-adrenergic receptors of CA1 in morphine-induced memory impairment.
Methods: Four experimental groups were used in this experimental study: 1)morphine, 2)clonidine and clonidine+morphine, 3) yohimbine and yohimbine+morphine, 4)yohimbine+clonidine+morphine. The total number of animals in these experiments was 208 adult male Wistar rats divided into 26 groups of 8. Morphine (4, 5, 6 mg/kg;i.p.) was used to induce memory impairment. Different doses of agonist and antagonist of α2-adrenergic receptors (clonidine and yohimbine) (1, 2, 4 μg/rat) were injected intoCA1. Shuttle box was used to study passive avoidance memory and ELISA was used to measure the levels of factors involved in mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM) in CA1.
Findings: Injection of an 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). Clonidine injection (4µg/rat) into CA1 enhanced 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 morphine-induced memory destruction (250.62±13.72 vs. 96.12±14.57) (p<0.001).Yohimbine injection (4 µg/rat) led to a decrease in memory compared to the saline group (161±19.69 vs. 241.38±15.20) (p<0.05) and its injection before the morphine (4 mg/kg) inhibited memory recall (113.12±13.9 vs. 241.5±21.59) (p<0.001). Injection of yohimbine (1 µg/rat) inhibited the response induced by clonidine and clonidine plus morphine in memory recall. Effective dose of morphine also decreased the 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 CA1 compared to the saline group (p<0.05). Injection of effective dose of clonidine before morphine increased the expression of these factors (p<0.05), while this increase was inhibited by injection of low dose of yohimbine.
Conclusion: The results showed that mitochondrial biogenesis and α2-adrenergic receptors of the hippocampal CA1 region may be involved in morphine-induced memory impairment. |
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| Keywords: Mitochondrial Biogenesis, α2-Adrenergic Receptors, Morphine, Memory Disorder. |
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Type of Study: Experimental |
Subject:
Physiology
Received: 2024/05/3 | Accepted: 2024/09/7
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