Inhibition of Hippocampal Astrocytic Connexin-43 Reduces the Naloxone-Induced Withdrawal Signs in Morphine Dependent Rats
Journal Title: The 1st Annual Meeting of Georgian Center for Neuroscience Research - Year 2020, Vol 2, Issue 20
Abstract
Background and Objective: Drug addiction is an ectopic form of learning, changes synaptic plasticity in various part of brain such as hippocampus. Morphine dependency cause a significant changes in the balance of excitatory and inhibitory neurotransmitters and altering Glutamate concentration Repeated morphine exposure affects Glial cells specifically astrocytes besides neurons. Gliotransmitter release and neurotransmitter uptake is the function of astrocytes by which keep the homeostasis of synaptic cleft. This has been demonstrated by a plethora of studies that morphine exposure would affect gliotransmitter synthesis and release factors. Astrocytic connexin-43 has a noteworthy role in gliotransmitter (specifically Glu) release into synaptic cleft and may affect synaptic transmission and synaptic plasticity. Consistent with these data, the hypothesis of hippocampal astrocytic connexin-43(CX-43) function in dependence and synaptic plasticity in male morphine treated rats is under investigation. Materials and Methods: Morphine (10 mg/kg, s.c.) was administered at an interval of 12 hours for 9 days. Then, morphine withdrawal syndrome precipitated by naloxone (1.5 mg/ kg, i.p.) was evaluated in rats receiving morphine with or without TAT-GAP19 (0.5 mmol/0.5 μl) as astrocytic connexin-43 inhibitor. Results: Animals receiving intrahippocampal microinjection of TAT-GAP19 60 min before each morphine administration, demonstrated a significant reduction in several signs of morphine withdrawal syndrome, including, scratching, ptosis, head tremor, freezing, sniffing, chewing, penis licking, defecation and teeth chattering. (unpaired t-test or Mann–Whitney U test, P<0.05, P<0.01, P<0.001). Pretreatment with TAT-GAP19 reduced other signs of withdrawal such as rearing and writhing. But the difference was not significant (unpaired t-test or Mann–Whitney U test, P>0.05). Conclusion: Obtained results showed that astrocytic connexin-43(CX-43) in the hippocampus may play role in different properties of morphine dependence.
Authors and Affiliations
Mahgol Darvish, Narges Hosseinmardi, Mahyar Janahmadi
Keywords
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- EP ID EP677952
- DOI 10.29088/GCNR-2020.43
- Views 170
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