Footshock facilitates discrimination of stimulus properties of morphine

We previously reported that stimulus properties of morphine can be assessed in a passive avoidance conditioning paradigm using a single dosing discrimination test. In this behavioral task, mice were trained to avoid electric footshock in a two-compartment shuttle-box by pairing morphine with shock in one compartment and saline with shock in the other compartment. In subsequent shock-free tests, animals can discriminate very well between saline and low doses of morphine on the one hand, and higher doses of morphine (close to that given during conditioning) on the other. Since only a single dose of morphine was presented on each test day, several days were needed to test different doses of the drug. We thus explored improving this technique by presenting different doses of morphine in a single day (cumulative dosing discrimination test). However, the animals did not dicriminate successfully between saline and morphine. Past studies have reported that mice utilize a "win-stay, lose-shift" strategy in their discrimination behavior. We hypothesized that the cumulative dosing test may have been subject to a "win-stay" bias. Accordingly, the initial exposure to the non-shock, i.e. saline, compartment promoted the animals to stay in this compartment until shock was administered. With the shock withheld throughout the test session, the "win-stay" strategy guided the animals to persevere in staying in this compartment. To confirm our hypothesis, a "lose-shift" condition through the presentation of a mild electric footshock was introduced during the test sessions. Results revealed a successful discrimination of stimulus properties of morphine, suggesting that the "lose-shift" strategy facilitated the discrimination of stimulus properties of morphine. These observations, taken together, would imply that the "win-stay, lose-shift" strategy may interact with the discrimination of the drug effects. Furthermore, the present results support the view that maintaining the environmental conditions, i. e. presence of a mild electric shock, across conditioning and test sessions can assist animals in retention of a learned task.