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.