NGF, BDNF and Arc mRNA Expression in the Hippocampus of Rats After Administration of Morphine
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Morphine can influence immediate early genes (IEG) of activity-regulated cytoskeletal-associated protein (Arc) and brain-derived neurotrophic factor (BDNF) which are activated in response to physiological stimuli during learning, as well as the nerve growth factor (NGF) gene which increases the expression of several IEGs for memory formation. The purpose of the current study was first to evaluate the effect of acute (1-day) and subchronic (15-days) morphine administration on memory retrieval of rats and second to determine the hippocampal expression of NGF, BDNF and Arc genes as potential contributors in the observed effects in each setting. The effects of morphine (intraperitoneal, 10, 15 and 20 mg/kg) on memory function and gene expression were assessed using inhibitory avoidance test and real-time polymerase chain reaction, respectively. We found that a single dose of morphine at the highest dose of 20 mg/kg decreases the post-training step-through-latency, while repeated administration of the same dose for 15 successive days increases this indicator of memory retrieval. We did not detect a significant change in the hippocampal expression of Arc, BDNF or NGF genes after a single episode of morphine treatment. However, subchronic morphine administration (15 and 20 mg/kg) increased the expression of Arc and BDNF genes in a dose dependent manner. A higher mRNA expression for the NGF was observed at the higher dose of 20 mg/kg. We hypothesize that the subchronic effects were morphine-induced behavioral sensitization which may have been enhanced through increased hippocampal Arc expression.
KeywordsMorphine NGF gene BDNF gene Arc gene Rat Memory
Compliance with Ethical Standards
Conflict of interest
There are no conflicts of interest associated with the present study.
All protocols for animal experiments were approved by the institutional animal Ethical Committee, Parand branch, Islamic Azad University, Parand, Iran.
- 16.Bojovic O, Bramham CR, Tjolsen A (2015) Chronic morphine treatment enhances sciatic nerve stimulation-induced immediate early gene expression in the rat dorsal horn. Acta Neurobiol Exp (Wars) 75(3):305–313Google Scholar
- 19.Lv X-F, Xu Y, Han J-S, Cui C-L (2011) Expression of activity-regulated cytoskeleton-associated protein (Arc/Arg3. 1) in the nucleus accumbens is critical for the acquisition, expression and reinstatement of morphine-induced conditioned place preference. Behav Brain Res 223 (1):182–191CrossRefGoogle Scholar
- 22.Zarrindast MR, Asadi F, Rezayof A (2011) Repeated pretreatment of morphine prevents morphine-induced amnesia: a possible involvement for dorsal hippocampal NMDA receptors. Arch Iran Med 14(1):32–38Google Scholar
- 24.Yoshii A, Constantine-Paton M (2010) Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol 70(5):304–322Google Scholar
- 44.Guzowski JF, Miyashita T, Chawla MK, Sanderson J, Maes LI, Houston FP, Lipa P, McNaughton BL, Worley PF, Barnes CA (2006) Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons. Proc Natl Acad Sci USA 103(4):1077–1082CrossRefGoogle Scholar
- 53.Manago F, Mereu M, Mastwal S, Mastrogiacomo R, Scheggia D, Emanuele M, De Luca MA, Weinberger DR, Wang KH, Papaleo F (2016) Genetic disruption of Arc/Arg3. 1 in mice causes alterations in dopamine and neurobehavioral phenotypes related to schizophrenia. Cell Rep 16 (8):2116–2128CrossRefGoogle Scholar