Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do nothave discriminative stimulus properties

The systemically active mixed inhibitor of enkephalin metabolism, N-((S)-2- benzyl-3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benz ylester (RB 120), alone or in combination with 4-{[2-[[3-(1H-indol-3-yl))-2 -methyl-1-oxo-2-[[(tricyclo[3.3.1.1.]dec-2-yloxy) carbonyl]amino}propyl]ami no]-1-phenylethyl]amino)-4-oxo-[ R-(R*, R*)]-butanoate N-methyl-D-glucamine (CI 988; CCK1 receptor antagonist) was investigated for discriminative and morphine generalisation effects using an operant drug discrimination parad igm in rats. Animals dosed with RE 120 (10 mg/kg) failed to develop a discr iminative response. Combined CI 988 (0.3 mg/kg) and RE 120 (10 mg/kg) also failed to elicit a discriminative response. Morphine-trained animals (3.0 m g/kg) did not generalise to RE 120 (10 and 20 mg/kg). Similarly, subsequent retraining of the same animals with 1.5 mg/kg of morphine did not elicit g eneralisation to RE 120 (10 or 20 mg/kg). Combined RE 120 (10 or 20 mg/kg) and CI 988 (0.3 or 3.0 mg/kg) treatment produced no notable drug lever sele ction in rats able to discriminate morphine (1.5 mg/kg) from saline. These results suggest that RE 120 may have low abuse potential at analgesic doses . (C) 2000 Published by Elsevier Science B.V.