DOI

https://doi.org/10.25772/2SCY-4Q39

Author ORCID Identifier

https://orcid.org/0000-0002-8324-3248

Defense Date

2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Integrative Life Sciences

First Advisor

Michelle Peace

Second Advisor

S. Stevens Negus

Third Advisor

Jose Eltit

Fourth Advisor

Amy Cadwallader

Fifth Advisor

Justin Poklis

Abstract

The epidemic of drug use in the United States and elsewhere in the world has resulted in tragic loss of life and substantial economic costs. Novel psychoactive substances (NPS) are one of the contributors to this problem, and the lack of information about many of these drugs compounds their risk. This dissertation proposes a strategy to use intracranial self-stimulation (ICSS) as a behavioral screening tool to assess emerging drugs of abuse for their abuse potential in order to generate a proactive threat assessment. A series of stimulant-type drugs including methcathinone, α-pyrrolidinohexanophenone (α-PHP), cocaine, and the phenyltropane analogs of cocaine WIN35428 and RTI-31 were evaluated using ICSS, and a bioanalytical method was developed to detect methcathinone and its metabolites in blood. ICSS predicted high abuse potential for methcathinone, novel methcathinone analogs, α-PHP, cocaine, and phenyltropane analogs of cocaine. The ICSS procedure was modified to account for pharmacokinetic differences resulting in different rates of drug onset and had sufficient resolution to distinguish between the rate of onset of cocaine, WIN-35428, and RTI-31. A preliminary chiral bioanalytical method was developed to quantify methcathinone and cathinone enantiomers in blood, and to qualitatively detect ephedrine, pseudoephedrine, norpseudoephedrine, phenylpropanolamine, and 4-hydroxyephedrine. Methcathinone and cathinone were detected in the blood, with a time course that correlated with the behavioral effects observed in ICSS testing and formed a counterclockwise hysteresis loop. ICSS appears to be an effective tool for an in vivo bioassay to screen emerging drugs of abuse for abuse potential, and appropriate bioanalytical methods should be developed to monitor the effectiveness of interventions.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-13-2022

Download

Share

COinS