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

Abstract

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 addictive-like 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.

• Authors: Negin Saeedi, Mahgol Darvishmolla, Zohreh Tavassoli, Shima Davoudi, Soomaayeh Heysieattalab, Narges Hosseinmardi, Mahyar Janahmadi, Gila Behzadi
• Journal: Brain and behavior (Brain Behav) Vol. 11 Issue 9 Pg. e2323 (09 2021) ISSN: 2162-3279 [Electronic] United States
• PMID: 34363739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.

Chemical References

• Excitatory Amino Acid Transporter 2
• Morphine

Topics

• Animals
• Excitatory Amino Acid Transporter 2 (metabolism)
• Hippocampus (metabolism)
• Male
• Morphine (pharmacology)
• Morphine Dependence
• Neuroglia (metabolism)
• Rats