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

Monika Trzcińska, Patricia Pimentel, James R. Stellar, Robert N. Hanson, Sung Woon Choi, David R. Elmaleh, Jianrong Zhang, K. R.C. Prakash, Amir P. Tamiz, Alan P. Kozikowski, Kenneth M. Johnson, Miles P. Smith, John W. Babich

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Six novel monoamine reuptake inhibitors were screened for their intrinsic effects on brain stimulation reward (BSR), as well as for their potential to reduce cocaine-induced reward-enhancement in that paradigm. Two of the compounds, nocaine-3B and 5-ara-74A (disubstituted piperidines) significantly reduced locus of rise (LOR), threshold measure of reward, at some doses. One compound, 1-RV-96A (a hybrid of the GBR and WIN-like agents) significantly reduced reward (increased LOR), but only at the highest dose tested. No effect of dose was found for MC9-20 (a GBR-like acyclic analogue of the N-bisarylmethoxyethyl-N′-phenylpropyl piperazine), nocaine-250B or 4-ara-42C (disubstituted piperidines). When cocaine (10 mg/kg, ip) and selected, hedonically neutral doses of novel compounds were combined, the following findings were obtained: MC9-20 (2.5 mg/kg, ip) showed a significant increase in cocaine-induced reward enhancement (0.2 log units or 53%). In contrast, nocaine-250B and 1-RV-96A (both at 10 mg/kg, ip) demonstrated a significant reduction (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 differences in the maximum behavioral output (MAX) at either dose of each of the six drugs, or when selected doses were combined with cocaine. These results indicate that nocaine-250B and 1-RV-96A constitute two potential anticocaine compounds worthy of further behavioral and biochemical evaluation.

Original languageEnglish (US)
Pages (from-to)171-180
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume68
Issue number1
DOIs
StatePublished - Apr 5 2001

Keywords

  • Anticocaine behavioral screen
  • Brain stimulation reward
  • GBR analogue
  • Phenyltropane
  • Piperazine
  • Piperidine
  • Reward threshold
  • WIN analogue

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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  • Cite this

    Trzcińska, M., Pimentel, P., Stellar, J. R., Hanson, R. N., Choi, S. W., Elmaleh, D. R., Zhang, J., Prakash, K. R. C., Tamiz, A. P., Kozikowski, A. P., Johnson, K. M., Smith, M. P., & Babich, J. W. (2001). Novel monoamine transporter ligands reduce cocaine-induced enhancement of brain stimulation reward. Pharmacology Biochemistry and Behavior, 68(1), 171-180. https://doi.org/10.1016/S0091-3057(00)00454-8