Date of Award

6-2022

Degree Name

Master of Science

Department

Psychology

First Advisor

Lisa Baker, Ph.D.

Second Advisor

Cynthia Pietras, Ph.D.

Third Advisor

Al Poling, Ph.D.

Keywords

Behavioral psychology

Access Setting

Masters Thesis-Open Access

Abstract

4-Methylenedioxymethamphetamine (MDMA) is currently under evaluation in phase III clinical trials as medication-assisted therapy for post-traumatic stress disorder (PTSD) and is expected to be approved by the FDA for clinical use in the near future. MDMA is also a popular abused substance with risks for cardiovascular toxicity and neurotoxicity, particularly when misused at higher doses. Characterization of the behavioral and neurochemical effects of novel psychoactive substances is an essential step in the development of safer alternative therapeutic agents. Drug discrimination is a preclinical behavioral assay with pharmacological specificity for characterizing in vivo drug actions in the central nervous system. This study implemented rodent drug discrimination to characterize the enantiomers of 5-(2-methylaminopropyl) benzofuran (5MAPB), 5-(2- methylaminobutyl) benzofuran (5-MBPB), and 6-(2- methylaminobutyl) benzofuran, benzofuran derivatives with potential MDMA-like effects. Eight male SpragueDawley rats were trained in a standard two-lever operant drug discrimination procedure under a fixed ratio 20 schedule of food reinforcement to discriminate MDMA (1.5 mg/kg) from saline. Once criteria for stimulus control were established, stimulus substitution tests were conducted with (RS) 5-MAPB, (R)-5-MAPB, (S)-5-MAPB, (R)-5-MBPB, (S)-5-MBPB, (R)-6-MBPB, and (S)-6-MBPB. All substances produced dose-dependent increases in MDMA-lever responding and full substitution at the highest dose assessed with minimal effects on response rate. The S- and R- enantiomers differed slightly in potency. These findings, considered together with in vitro neurochemical assays, indicate the benzofuran scaffold is a viable candidate for development of medications with MDMA-like therapeutic effects and reduced toxicities.

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