Evaluating the Effects of Estradiol Valerate and Raloxifene towards Morphine State-Dependent Learning in Mice

Aims: The aim of this study was to evaluate the possible effects of estradiol valerate and a specific estrogen receptor modulator, raloxifene on passive avoidance learning in male mice and to determine whether there is an interaction between estrogen receptor binding drugs and morphine.
Study Design: In this study, the state-dependent learning for morphine was evaluated at the first step, and then the effects of raloxifene and estradiol on this characteristic of morphine was evaluated. Besides the later two drugs’ independent effect on passive avoidance learning was studied too.
Place and Duration of Study: All the experiments carried out in the pharmacology laboratory, School of Pharmacy, Zanjan University of Medical Sciences between April-July 2013.
Methodology: In this study, 120 Male NMRI mice were used according to the guidelines for animal ethics. State dependent learning (as one of the usual methods for assessment of passive avoidance learning) was performed using a step down shuttle box. During training, mice were shocked only after they step down on from the queue. Latencies to step down are recorded to assess passive avoidance short term memory. Prior training they received saline or morphine and before testing session the animals received saline or morphine plus estrogen valerate or raloxifene in relevant groups.
Results: The results illustrated that pre-training administration of morphine, induced amnesia which was retained by a similar pre-test dose (morphine state dependent learning). Pre-test estradiol valerate injection was able not only to retrieve morphine induced amnesia but also improved morphine state-dependent learning. On the other hand, raloxifene had no effect on memory retrieval itself, but decreased morphine state dependent learning.
Conclusion: The results of this study indicated that estrogen receptor modulators not only are able to manipulate the learning patterns, but also there might be an interaction between these drugs and morphine induced state dependent learning in mice.