Reinforcing effects of the enkephalin analogs, EK-209 and EK-399, in rats

The reinforcing 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 by means of a self-administration technique with rats. The animals were trained to self-administer an intravenous dose of morphine by a lever-press response. A test drug was substituted for morphine after the rats had initiated and maintained its self-administration. When codeine, fentanyl, pentazocine or EK-209 was available, most of the rats increased the number of self-administrations as the unit dose of these drugs was decreased. When levallorphan or EK-399 was available, most of the rats did not increase responding; only one of 4 rats slightly increased the number of self-administrations as the unit dose of EK-399 was decreased. These results indicate that EK-209, like codeine, fentanyl, and pentazocine, possesses a reinforcing effect, whereas EK-399, like levallorphan, has a very weak effect, suggesting that the latter compound possesses low abuse liability.