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Psychopharmacology Lab 4400 Massachusetts Avenue NW Washington, DC 20016 United States

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Hayley Manke

Hayley Manke

hm2522@student.american.edu

Curriculum Vitae

I am a second year doctoral (PhD) student in the Behavior, Cognition, and Neuroscience program. I graduated from American University in spring of 2019 with my BA in psychology. Over the course of my undergraduate career, I worked in the Psychopharmacology Laboratory led by Dr. Anthony L. Riley at American University in Washington, D.C. I primarily assisted on work that characterized the affective properties of synthetic cathinones (i.e., bath salts), specifically alpha pyrrolidinopentiophenone (α-PVP). I co-authored a study investigating sex differences in the rewarding and aversive effects of α-PVP, as well as assisted on a project that examined the impact of the enantiomers of α-PVP in its rewarding and aversive properties.

My main research interests lie in the different ways that drugs may impact behavior and factors that contribute to abuse vulnerability of a given compound. Factors that may impact abuse liability include, but are not limited to, dose, route of administration, sex, age, drug history and strain. I focus on these areas in traditional psychostimulants and the synthetic cathinones which are synthetic analogs of cathinone, an amphetamine-like stimulant. Cathinone is found in the leaves of the khat plant (Catha edulis), native to Africa and the Arabian Peninsula. Recently, I have shifted my focus from α-PVP to more traditional psychostimulants (e.g., amphetamine) as well as another bath salt that emerged in the early 2000s, i.e., methylone. Methylone is a psychostimulant similar to MDMA (with the exception of its affinity for the serotonin transporter) in that it acts as a reuptake inhibitor and substrate releaser of dopamine, norepinephrine and serotonin.

Our lab examines the affective properties of these compounds using animal models. Typically, reward is described as driving the abuse of a particular drug. However, we postulate that the balance between the rewarding and aversive effects of a drug mediate its abuse. As such, investigating the rewarding and aversive effects of a compound allows for better predictions of abuse liability. My first study in a two-part investigation examined conditioned taste avoidance, hyperthermia and hyperactivity induced by 5.6, 10 and 18 mg/kg of methylone in male and female rats. The results of the study demonstrated that the aversive effects of methylone, in some cases (e.g., CTA, thermoregulatory effects and hyperactivity), were sex dependent. As a result of methylone showing some sex-dependent effects, we think it is important to investigate how other factors (e.g., drug history) shift the affective balance and how sex may impact the overall drug history effect.

Drug history is another factor not well documented for synthetic cathinones that may contribute to their use and abuse. As such, an ongoing project analyzes the effects of methylone pre-exposure on MDMA, MDPV and fluoxetine-induced conditioned taste avoidance as well as sex differences in these effects. In previous work done by our lab, we showed that MDPV pre-exposure attenuated the aversive effects of itself and cocaine (see Woloshchuk et al., 2017). These results are consistent with the neurochemistry of these two compounds in that they are both a potent dopamine reuptake inhibitor, which has been highly implicated in the aversive effects of cocaine (Serafine & Riley 2013). Accordingly, it is expected that methylone will attenuate MDMA-induced aversions and have no effect on MDPV. Given their shared effects on serotonin, fluoxetine-induced aversions may be partially attenuated.

As mentioned above, I am also interested in amphetamine. I am preparing to conduct a study that will assess the effects of 6c, a protein kinase C (PKC) inhibitor, administration on amphetamine-induced neurotoxicity (measured by changes in catecholamine synthesis, levels and reuptake in female C57BL/6 mice). Previous studies have shown that PKC inhibitors are able to block dopamine release and locomotor effects of cocaine (Zestos et al., 2018) and amphetamine (Carpenter et al., 2017). Amphetamine has clear neurotoxic effects as evidenced in changes in enzymes involved in the synthesis and reuptake of catecholamines in the brain. Although these neurotoxic changes accompanying the acute and chronic use of amphetamine are well characterized, no treatment exists for the neurotoxicity associated with its use. This upcoming study aims to assess a potential treatment modality that targets the reversal of amphetamine’s neurotoxic effects focusing on protein kinase C that is activated by amphetamine which, in turn, induces a cascade of effects on catecholamine levels in the brain. Following this study, the goal is to examine the ability of 6c to impact the intravenous self-administration of various psychostimulants (cocaine, amphetamine, bath salts, etc).