The state dependency effect of morphine on memory by behavioral and electrophysiological methods in freely moving rats

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Abstract

Endogenous opioid system agonists exert amnestic effects in different models of memory. It has been suggested that these amnestic effects may be linked indirectly to state-dependent learning. Accordingly pre-training administration of morphine can impair the retrieval of learned tasks in a state dependent manner, which is reversible by pre test morphine administration. In this study, state dependency effect of morphine was investigated by behavioral and electrophysiological methods in freely moving rats. In behavioral studies the step-down passive avoidance paradigm for examining long term memory was used. Also, because of involvement of hippocampus in memory, the possible role of hippocampal dentate gyrus neurons in morphine state dependency was assessed using electrophysiological method. In electrophysiological studies, field excitatory post-synaptic potential (fEPSP) and population spike (PS) were recorded from dentate gyrus of freely moving rats. Results of step-down showed that different doses of morphine (1, 5, 10, and 15 mg/kg, i.p.) could induce significant state dependency in rat, but could not induce significant changes in the slope of fEPSP and PS amplitude of freely moving rats in contrast to the control group. In conclusion, it seems that granular cells of hippocampal dentate gyrus are not involved in morphine state dependency, and other areas of hippocampus or other brain structures may be involved in this phenomenon, which needs further investigation.