Hippocampal glial cells modulate morphine-induced behavioral responses

Seyedaghamiri, Fatemehsadat; Heysieattalab, Soomaayeh; Hosseinmardi, Narges; Janahmadi, Mahyar; Elahi-Mahani, Azadeh; Salari, Farhad; Golpayegani, Mehdi; Khoshbouei, Habibeh

doi:10.1016/j.physbeh.2018.04.003

Cited by 8 publications

(5 citation statements)

References 76 publications

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“…Spinal cord-associated jumping was attenuated while rearing, wet dog shakes and paw tremor were not significantly altered. The observed effects could also be at least partly associated with GRs localized in Cx30-positive glia in the hippocampus, where the targeting of our model is evident [Tertil et al 2018], in line with the observations of Seyedaghamiri (2018) showing effects of local glial inhibition in the CA1 region.…”

supporting

confidence: 89%

“…1g). This attenuation of the somatic expression of withdrawal directly confirms a role of astrocytic GR in morphine addiction that could be hypothesized from previous studies utilizing the non-specific inhibition of glial cell metabolism or pharmacological antagonists of GR [Navarro-Zaragoza et al 2012, Seyedaghamiri et al 2018. It has to be noted that other withdrawal symptoms remained similar in both control and GR astroKO mice, which may perhaps be due to the limited efficiency of our Cx30-CreERT2-driven knockout model, as demonstrated by the gene expression data.…”

supporting

confidence: 83%

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Astroglial Knockout of Glucocorticoid Receptor Attenuates Morphine Withdrawal Symptoms, but Not Antinociception and Tolerance in Mice

et al. 2021

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The development of tolerance and drug dependence limit the clinical application of opioids for the treatment of severe pain. Glucocorticoid receptors (GRs) are among molecular substrates involved in these processes. Most studies focus on the role of neuronal GR, while the involvement of GR on glial cells is not fully understood. To address this issue, we used a transgenic model of conditional GR knockout mice, targeted to connexin 30-expressing astrocytes, treated with repeated doses of morphine. We observed no difference between control mice and astrocytic GR knockouts in the development of antinociceptive tolerance. Nevertheless, when animals were subjected to precipitated withdrawal, knockouts presented some attenuated symptoms, including jumping. Taken together, our data suggest that hippocampal and spinal astrocytic GRs appear to be involved in opioid withdrawal, and drugs targeting the GR may relieve some symptoms of morphine withdrawal without influencing its antinociceptive properties.

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supporting

confidence: 89%

supporting

confidence: 83%

Astroglial Knockout of Glucocorticoid Receptor Attenuates Morphine Withdrawal Symptoms, but Not Antinociception and Tolerance in Mice

et al. 2021

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“…In addition to neurons, glial cells, especially astrocytes, are involved in glutamate release and uptake and also in side effects of chronic opioid exposure, including tolerance and dependence (Mahmoud & Gharagozloo, 2019;Miguel-Hidalgo, 2009). Our previous studies reported that glial cells in the hippocampus may play role in dependence (Seyedaghamiri & Heysieattalab, 2018). Besides the presence of morphine receptors on neurons, the mu-opioid receptor which seems to mediate the euphoric effects of opioids, is widely expressed in hippocampal astrocytes (Nam & Han, 2018) Therefore, glial cells appear to be involved in morphine-induced metaplasticity and consequent behavioral changes.…”

Section: Introductionmentioning

confidence: 99%

The role of hippocampal glial glutamate transporter (GLT‐1) in morphine‐induced behavioral responses

et al. 2021

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Opioid abuse modifies synaptic plasticity, which leads to behavioral changes, such as morphine dependence, but the mechanism remains poorly understood. Glial cells play an important role in the modulation of synaptic plasticity and are involved in addictivelike behaviors. The indisputable role of glutamate in opiate addiction has been shown.Astrocytes, a type of glial cells, which are integral functional elements of synapses, modulate the concentration of glutamate in the synaptic space. One of the most important mechanisms for glutamate concentration regulation is its uptake from the synaptic cleft. In this study, we evaluated the role of hippocampal glial glutamate transporter (GLT-1) in morphine dependence. Male rats received subcutaneous (s.c.) morphine sulfate (10 mg/kg) at an interval of 12 h for 9 days. In order to activate GLT-1, animals received an intrahippocampal injection of ceftriaxone (0.5 mmol/0.5 μl) in the CA1 region of the hippocampus, 30 min before each morphine administration. Rats were assessed for morphine dependence by monitoring naloxone hydrochloride-induced morphine withdrawal. Our results showed that hippocampal microinjection of ceftriaxone, as an activator of GLT-1, reduced some signs of morphine withdrawal, such as activity, diarrhea, head tremor, freezing, and ptosis. It seems that hippocampal GLT-1 can be affected by chronic morphine administration and involved in morphine dependence. Therefore, its activation may reduce morphine side effects by reducing hippocampal glutamate.

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“…In response to its role in synaptic strength, the glial cell promotes the release of glutamate that was triggered by exposure to morphine [46]. Chronic exposure to morphine modulates the adaptation of glutamatergic transmission in the brain, altering the α-amino-3hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors [47].…”

Section: Synaptic Plasticity: Ltp and Ltdmentioning

confidence: 99%

Molecular Basis for Morphine Addiction

Suliman,

Abu Bakar,

Othman

2023

MJMHS

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Opioids are known to be used medically as analgesia and illegally as recreational drugs. Morphine, a semi-synthetic opioid is used widely in managing pain. Despite knowing the side-effect of the usage, the number of illegal users of opioids or morphine, specifically, is statistically still growing. Long-term usage of opioids, especially morphine, induces addiction that is expressed as dependence, tolerance, and withdrawal behaviour. Currently, with expanding research on anti-addiction studies, many loopholes in the basic mechanism of addiction were found, providing a setback for the researchers to overcome the problem. Thus, this review is aimed to present the latest update on the cellular modifications caused by chronic morphine treatment. By understanding and updating the knowledge, research can focus on the recent postulation and suggestions.

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Hippocampal glial cells modulate morphine-induced behavioral responses

Cited by 8 publications

References 76 publications

Astroglial Knockout of Glucocorticoid Receptor Attenuates Morphine Withdrawal Symptoms, but Not Antinociception and Tolerance in Mice

Astroglial Knockout of Glucocorticoid Receptor Attenuates Morphine Withdrawal Symptoms, but Not Antinociception and Tolerance in Mice

The role of hippocampal glial glutamate transporter (GLT‐1) in morphine‐induced behavioral responses

Molecular Basis for Morphine Addiction

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