Morphine's effects on learning and memory processes are well known to depend on synaptic plasticity in the hippocampus. Whereas the role of the hippocampus in
morphine-induced
amnesia and state-dependent learning is established, the biochemical and molecular mechanisms underlying these processes are poorly understood. The present study intended to investigate whether administration of
morphine can change the expression level of rat hippocampal
proteins during learning of a passive avoidance task. A step-through type passive avoidance task was used for the assessment of memory retention. To identify the complex pattern of
protein expression induced by
morphine, we compared rat hippocampal
proteome either in
morphine-induced
amnesia or in state-dependent learning by two-dimensional gel electerophoresis and combined mass spectrometry (MS and MS/MS). Post-training administration of
morphine decreased step-through latency. Pre-test administration of
morphine induced state-dependent retrieval of the memory acquired under post-training
morphine influence. In the hippocampus, a total of 18
proteins were identified whose MASCOT (Modular Approach to Software Construction Operation and Test) scores were inside 95% confidence level. Of these, five hippocampal
proteins altered in
morphine-induced
amnesia and ten
proteins were found to change in the hippocampus of animals that had received post-training and pre-test
morphine. These
proteins show known functions in cytoskeletal architecture, cell metabolism,
neurotransmitter secretion and neuroprotection. The findings indicate that the effect of
morphine on memory formation in passive avoidance learning has a morphological correlate on the hippocampal
proteome level. In addition, our proteomicscreensuggests that
morphine induces memory impairment and state-dependent learning through modulating neuronal plasticity.