I graduated from the University of Houston in 2012 with my BS in Psychology. During my undergraduate career I volunteered to work with both the Clinical Neuroscience Research Team led by Dr. Merrill Hiscock and the Behavioral Neuroscience Research Team directed by Dr. J. Leigh Leasure. In spring of 2013 I began working as a research technician in Dr. M. Waleed Gaber’s Pediatric Oncology/Radiation Research Lab through the Baylor College of Medicine at Texas Children’s Hospital in Houston, Texas. In the fall of 2015 I joined the Psychopharmacology Laboratory led by Dr. Anthony (Tony) L. Riley at American University in Washington, DC, as a Psychology Master’s Student in the Biological/Experimental thesis track. After successfully defending my Master’s thesis during the summer of 2017, I joined the doctoral program (PhD) in Behavior, Cognition and Neuroscience (BCaN) in the fall of 2017. I have an expected graduation date in May of 2021.
My goals involve understanding the way drugs affect behavior; including drug taking, use, and abuse, as well as researching factors that may influence addiction vulnerability. Some factors that may impact abuse liability include: age, sex, dose, route of administration, drug history, species, strain, concurrent and simultaneous drug use, among a large list of other factors. My work throughout my graduate career has been focused on characterizing the synthetic cathinones, specifically alpha-pyrrolidinopentiophenone (α-PVP). α-PVP is a psychostimulant that is cocaine-like in its mechanism of action in that it is a pure reuptake inhibitor for dopamine (DA), norepinephrine (NE) at their respective transporters, but does not block the reuptake of serotonin (5-HT) and does not stimulate the release of these neurotransmitters (as is the case with amphetamine and amphetamine-like drugs).
Synthetic cathinones (i.e. “bath salts”, “research chemicals”, “legal highs” etc.) are man-made analogs of cathinone, a naturally derived amphetamine-like stimulant. Cathinone is found in the fresh leaves of the khat plant (Catha edulis) which is a small leafy green shrub native to eastern Africa (Ethiopia, Kenya, etc.) and the Arabian Peninsula where the leaves are chewed or brewed in teas for their mild stimulant effects.
Our lab predominantly focuses on the affective properties of these compounds. Drug use and abuse are thought to be a function of an affective balance, such that rewarding effects of the drug support intake while its aversive effects limit it. The studies I have performed recently have focused on behavioral assays that index these affective properties and employed designs such as conditioned taste avoidance (CTA) (assesses aversive qualities) and conditioned place preference (CPP) (assesses rewarding qualities). CTA takes advantage an animal’s tendency to avoid consumption of ordinarily preferred drug-paired solutions (i.e., water sweetened with saccharin), presumably due to an association between the taste (the conditioned stimulus, CS) and the drug’s aversive effects (the unconditioned stimulus, US). CPP is used as a measure for reward as the animal associates a distinct environment with a drug’s rewarding effects and spends more time in the drug-paired environment. These experimental designs are used both separately and in tandem (a combined CTA/CPP design) to assess the balance of reward and aversion associated with α-PVP, which are factors that ultimately impact the likelihood of self-administration – the gold standard in determining abuse potential in human users. In addition to these assays I have assessed the effects that α-PVP may have on hyperactivity and thermoregulation (effects that contribute to toxic reactions in humans, e.g., potentially fatal increases in body temperature and extreme tremor disorder or excited delirium).
Although α-PVP is becoming characterized in relation to its rewarding and aversive properties, factors that impact these effects (and their relative balance and abuse potential; see Riley 2011; Verendeev and Riley 2013) have received little attention. In that context, my dissertation will involve a series of experiments which will address the relative contributions of the R- and S-enantiomers of α-PVP to neurochemical (the reuptake of the brain amines), physiological (hyperthermia) and behavioral (taste avoidance and activity) effects produced by the racemic mixture (50:50 ratio of each enantiomer). In addition, sex as a biological variable on these effects and the impact of drug history (e.g., alcohol, nicotine and THC) on the subsequent behavioral responsivity to α-PVP will be examined
The first set of projects involved the stereoselective effects of α-PVP. Enantiomers are structural isomers of a molecule which are mirror images of each other that cannot be superimposed. Enantiomers can have differential effects. The goal of this project was to determine the relative contribution of each enantiomer of racemic α-PVP in terms of their aversive effects. The findings of this work was recently published in a special issue of synthetic cathinone research featured in the journal Psychopharmacology (see Nelson et al., 2019a).
The second phase of experiments compared the effects of the enantiomers and their contribution to the racemate in terms of locomotor activity, thermoregulation and the neurochemical effects of α-PVP. This data is currently being prepared for publication.
The third project was a comparison of adult male and female Sprague Dawley rats in a combined CTA/CPP design. We also assessed temperature and activity effects to determine differences in toxicity. The logic for this project was that biological sex is a factor known to impact the balance of aversive and rewarding drug effects and ultimately influence abuse liability. This project was recently accepted for publication in Pharmacology Biochemistry and Behavior August 2019 (Nelson et al., 2019b).
The fourth and final piece of my dissertation will be to determine the impact of a prior drug experience, or drug pre-exposure, on the rewarding and aversive effects of α-PVP. The drugs chosen to assess the effects of drug pre-exposure on α-PVP’s rewarding and aversive effects are nicotine, THC and ethanol (due to their relative ease of procurement by human users and the likelihood that these drugs are already being used by those who also use bath salts; see Benschop et al., 2017; Elliot and Evans, 2014; Mohr et al., 2018; Palamar, 2015) in adult male Sprague-Dawley rats using a combined CTA/CPP design. Data collection is projected to begin late Fall 2019 or early Spring 2020.
Assessing the stereospecificity of the neurochemical (Experiment 1), physiological and behavioral (Experiment 2) effects of α-PVP, as well as subject (sex; Experiment 3) and experiential (drug history; Experiment 4) factors impacting α-PVP, should provide additional characterization of this specific bath salt that may yield better understanding of its abuse liability and possible prevention and/or treatment.