Discriminative stimulus effects of enkephalin analogs, EK-209 and EK-399, in rats

The discriminative stimulus effects of two enkephalin analogs, Tyr-D-Ala-Gly-MePhe-NHNHCOCH2CH3.AcOH (EK-209) and Tyr-D-Met(O)-Gly-EtPhe-NHNHCOCH3.AcOH (EK-399), were assessed in a drug discrimination experiment with rats. The animals were trained to discriminate between the effect of morphine (3 mg/kg s.c.) and saline in a two-lever choice, water reinforced procedure. After the discrimination training had been completed, the animals were used in stimulus generalization tests. A test drug was administered subcutaneously before the test session, and the animals were allowed to select the morphine or saline lever. The animals completely generalized to the effects of codeine, fentanyl and EK-209, but did not generalize completely to the effect of ethylketocyclazocine. After receiving an injection of pentazocine, levallorphan, N-allynormetazocine, or EK-399, the animals pressed the morphine lever, but did not generalize completely to the effects of these drugs. These results suggest that the discriminative stimulus effect of EK-209 is similar to that of morphine, whereas the effect of EK-399 may be different from that of morphine.