Date of Award

8-2016

Degree Name

Doctor of Philosophy

Department

Psychology

First Advisor

Dr. Lisa E. Baker

Second Advisor

Dr. Alan D. Poling

Third Advisor

Dr. Bradley E. Huitema

Fourth Advisor

Dr. Adam J. Prus

Keywords

Drug discrimination, MDPV, methylenedioxypyrovalerone, stimulus effects 4-methylmethcathinone, 3, 4 - mephedrone, discriminative

Abstract

Recent escalation in the popularity of recreational synthetic cathinone (“bath salts”) use has prompted numerous scientific investigations of the neurochemical and behavioral effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (4-MMC), two of the more common chemical constituents of these illicit “bath salts”. Previous neurochemical and electrophysiological studies have revealed that MDPV functions as a blocker, and 4-MMC as a substrate, at monoamine transporters, and both produce transient increases in extracellular monoamines. In addition, previous research has demonstrated that MDPV and 4-MMC support self-administration in nonhuman experimental subjects, and their rewarding effects are observed when paired with contextual cues in nonhuman models of conditioned place preference. Comparatively fewer studies have characterized the discriminative stimulus effects of these drugs using drug discrimination methods. The drug discrimination paradigm is an in vivo drug-detection assay with high predictive validity. To further characterize the discriminative stimulus effects of these synthetic cathinones, the current study trained 16 male Sprague-Dawley rats to discriminate either 0.3 mg/kg MDPV (N = 8) or 1.0 mg/kg 4-MMC (N = 8) from saline.

Once the rats met discrimination acquisition criteria, substitution tests were conducted with compounds that function as dopamine releasers (d-amphetamine, (+)-methamphetamine), monoamine transporter inhibitors (MDPV, (-)-cocaine), monoamine transporter releasers (4-MMC, MDMA), a serotonin releaser ((+)-fenfluramine), and an indoleamine hallucinogen (lysergic acid diethylamide, (+)-LSD). Discriminative stimulus control was established in ~35 and ~37 training sessions in the 0.3 mg/kg MDPV group and 1.0 mg/kg 4-MMC group, respectively. In the 0.3 mg/kg MDPV training group, the aforementioned dopamine releasers, monoamine transporter inhibitors, and (+)-fenfluramine produced full substitution, whereas the monoamine transporter releasers and (+)-LSD failed to fully substitute and produced statistical reductions in response rate. In the 1.0 mg/kg 4-MMC training group, all drugs except (+)-LSD and (+)-fenfluramine produced full substitution. Overall, these findings are consistent with human user reports indicating that MDPV and 4-MMC produce interoceptive stimulus effects that are comparable to prototypical drugs of abuse, such as cocaine and MDMA. Future studies with receptor-selective antagonists would be especially valuable to further investigate the neurochemical actions contributing to the discriminative stimulus effects produced by these substances.

Access Setting

Dissertation-Open Access

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