Novel monoamine transporter ligands reduce cocaine-induced enhancement of brain stimulation reward

Six novel monoamine reuptake inhibitors were screened for their intrinsic e ffects on brain stimulation reward (BSR), as well as for their potential to reduce cocaine-induced reward-enhancement in that paradigm. Two of the com pounds, nocaine-3B and 5-ara-74A (disubstituted piperidines) significantly reduced locus of rise (LOR), threshold measure of reward, at some doses. On e compound, 1-RV-96A (a hybrid of the GBR and WIN-like agents) significantl y reduced reward (increased LOR), but only at the highest dose tested. No e ffect of dose was found for MC9-20 (a GBR-like acyclic analogue of the N-bi sarylmethoxyethyl-N ' -phenylpropyl piperazine). nocaine-250B or 4-ara-42C (disubstituted piperidines). When cocaine (10 m/kg, ip) and selected, hedon ically neutral doses of novel compounds were combined, the following findin gs were obtained: MC9-20 (2.5 mg/kg, ip) showed a significant increase in c ocaine-induced reward enhancement (0.2 log units or 53%). In contrast, noca ine-250B and 1-RV-96A (both at 10 mg/kg, ip) demonstrated a significant red uction (0.13 log units or 41%) in cocaine-induced reward enhancement (P<.01 and P<.05, respectively). as measured by changes in LOR. There were no dif ferences in the maximum behavioral output (MAX) at either dose of each of t he six drugs, or when selected doses were combined with cocaine. These resu lts indicate that nocaine-250B and I-RV-96A constitute two potential antico caine compounds worthy of further behavioral and biochemical evaluation. (C ) 2001 Elsevier Science Inc. All rights reserved.