Preclinical Abuse Liability Screening of Designer Psychostimulant Mixtures

Western Michigan University, Kalamazoo MI

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Abstract

? DESCRIPTION (provided by applicant): Athinone derivatives (bath salts) have similar neurochemical actions and produce comparable behavioral effects to other psychostimulants. In particular, these substances influence the activities of the brain reward pathways implicated in substance abuse and addiction. The proposed research plan will investigate 4-methylmethcathinone, also known as mephedrone (MEPH) and methylenedioxypyrovalerone (MDPV) alone and in combination with other drugs of abuse (e.g., cocaine, MDMA, amphetamine) and in combination with stress using the following validated preclinical assessments predictive of abuse liability: behavioral sensitization (BS), conditioned place preference (CPP), and drug discrimination (DD). The DD paradigm is a predictive model of the neurochemical actions responsible for the subjective effects of psychoactive drugs. As such, DD methods will primarily be utilized for the first specific aim to investigate the specific neuropharmacological actions involved in the discriminative stimulus functions of MEPH and MDPV and to determine if other psychostimulants potentiate the discrimination of these substances. For the second specific aim, BS and CPP methods will be utilized to determine if concurrent exposure to MEPH or MDPV with other psychostimulants enhances behavioral responses indicative of abuse liability. Finally, the third specific aim will implement BS and CPP methods to examine combined exposure to restraint stress and MEPH or MDPV in an effort to determine if the abuse liability of these substances is enhanced by the physiological correlates of stress. This research will contribute new information to the substance abuse literature and expand on current knowledge regarding the biobehavioral profile of methcathinone derivatives. As an AREA grant application, a major goal of this project is to engage students in research and discovery. Recent studies indicate that illicit methc Consistent with our university's mission to b learner centered, discovery driven, and globally engaged, students will participate in the design and implementation of experimental methodology, data analysis, manuscript preparation, and research poster presentations at conferences. Involving students in these research activities will strengthen and enhance the university's research environment. The opportunity to publish novel scholarly research will strengthen the students' prospective research careers.