NGF, BDNF and Arc mRNA Expression in the Hippocampus of Rats After Administration of Morphine.

Abstract

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 20mg/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 20mg/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 20mg/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 20mg/kg. We hypothesize that the subchronic effects were morphine-induced behavioral sensitization which may have been enhanced through increased hippocampal Arc expression.