Enhancing Hippocampal Neuronal Numbers in Morphine-Dependent Rats by Voluntary Exercise Through a Brain-Derived Neurotrophic Factor-Mediated Mechanism

Abstract

Background: Exposure to morphine decreases neurogenesis in the hippocampus. Recent studies have shown that voluntary running decreases the severity of anxiety behaviors and cognitive deficits, and increased synaptic plasticity in morphine-dependent rats. Objectives: This study aimed to investigate whether the morphine dependence-induced attenuation of hippocampal neuron number in rats would be reversed by voluntary running through a brain-derived neurotrophic factor (BDNF)-mediated mechanism. Materials and Methods: The rats were received injections of 10 mg/kg of morphine twice a day over ten days of voluntary running. A specific antagonist of BDNF action (TrkB-IgG) was used to block the hippocampal BDNF action during the study period; cytochrome C (Cyt C) was used as the control drug. Results: We found that chronic exposure to morphine had decreased the number of dentate gyrus neurons in sedentary rats receiving Cyt C or IgG in comparison to the control rats (P < 0.05). Moreover, exercise groups receiving saline or morphine showed an increase in the number of neurons following ten days running; blocking the BDNF action with TrkB-IgG fully inhibited this effect (both, P = 0.0001). Conclusions: This study demonstrates that that voluntary exercise can ameliorate the attenuation of hippocampal neuron number induced by morphine dependence through a BDNF-mediated mechanism. Thus, physical activity might have a potential role in ameliorating chronic morphine-induced neuronal changes in the hippocampus.

Effect of exercise and morphine on psychological and physical dependencies, BDNF and TrkB gene expression in rat’s hippocampus

“…Our findings are similar to many studies 23 , 25 , 26 providing evidence that exercise can increase the BDNF and TrKB levels in hippocampus of morphine-dependent rats. Identical to previous studies, 27 , 28 our study supported that BDNF acts via the TrKB receptor is an important mediator between exercise and neural functions and play a key role in cell survival, neurite outgrowth, function of adult neurons, differentiation of developing neurons, learning and memory for morphine administration, 29 and protects against neurodegenerative disorders.…”

The effect of different exercise training modes on dentate gyrus neurodegeneration and synaptic plasticity in morphine-dependent rats

“…In addition, exercise training facilitates the induction of LTP by lowering the LTP induction threshold [33]. Regular exercise training prevents the decrement of the hippocampal DG neuron numbers induced by the injection of morphine through a brain-derived neurotrophic factor (BDNF)-mediated mechanism [36].…”

Effects of gallic acid and physical exercise on passive avoidance memory in male rat

“…The presence of GABAergic receptors in the basolateral amygdala raises the probability of their role in memory storage in this region. Rashidy-Pour et al (2015) studied the role of the GABAergic system in acquiring, consolidating, and retrieving the newly learned information in the spatial avoidance learning model, and observed that parenteral GABA agonist (muscimol) significantly impaired the storage and retrieval of spatial memory (Rashidy-Pour, Vafaei, 2001). (Mansouri et al 2014) studied the potential mechanism of gallic acid anxiolytic effects in rat using plus maze test.…”

“…Nutrophen enhances the viability and regeneration of the neurons, causes enhancement, stimulation, and growth of these cells, and is essential for memorization and memory (Maass et al, 2016). Neurotrophic factors such as brainderived neurotrophic factor (BDNF), nerve growth factor, and fibroblast growth factor contribute to support and growth of different types of cerebral neurons (Rashidy-Pour, Fathollahi et al, 2015).…”

“…This factor is from family neurotrophins that helps to expand neural network. BDNF is one of the most important members of this family and causes launching of intracelluar cascades and eventually production and differentiation of new neurons (Rashidy-Pour, Fathollahi et al, 2015). This factor serves as a mediator of synaptic effects, neural bindings, and plasticity in the brain.…”