Hayley Manke

I am a fourth year doctoral (PhD) student in the Behavior, Cognition, and Neuroscience program. I have graduated from American University with my BA and MA in psychology. Over the course of my undergraduate and graduate careers, I have worked in the Psychopharmacology Laboratory led by Dr. Anthony L. Riley at American University in Washington, DC, investigating the impacts of drugs on the brain and behavior. My main research interests lie in examining the affective properties (i.e., reward, reinforcement, aversion) of drugs and factors that contribute to abuse vulnerability of a given compound. The Psychopharmacology Lab examines the affective properties of drugs of abuse 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 use and abuse. Further, several experiential and subject factors may impact such abuse liability, such as dose, route of administration, sex, age, drug history and strain. As such, investigating the rewarding and aversive effects of a compound and factors impacting these properties allows for better predictions of abuse liability.
I focus on these areas in traditional psychostimulants and the synthetic cathinones which are synthetic analogs of cathinone, an amphetamine-like stimulant. Since beginning in the lab, I have studied the synthetic cathinones (α-PVP, MDPV, methylone, eutylone) and more traditional psychostimulants (e.g., amphetamine, cocaine, MDMA). In one of my first studies, I conducted a two-part investigation examining 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. In this context, I recently demonstrated that there are sex differences in the effects of methylone pre-exposure on the aversive effects of MDPV and MDMA. In males, methylone pre-exposure attenuated the aversive effects of both compounds, whereas in females, methylone pre-exposure only attenuated the aversive effects of MDPV. Moreover, the strongest attenuation was observed with MDPV. These findings implicate a commonality between the aversive effects of methylone and MDPV, although additional studies are needed to explore this further. Additionally, such an attenuation of MDPV and MDMA- induced aversive effects has implications for the abuse potential of these compounds as decreased aversive effects impacts the overall affective balance which may impact the use of these compounds.
Recently, I have started my dissertation projects which will focus on the novel synthetic cahtinon eutylone. Eutylone has become increasingly prevalent in forensic reports and in EDM scenes since 2019. Given its popularity on the drug market, it is imperative to examine its rewarding and aversive effects. This is especially true given eutylone’s mechanistic and structural similarities to other bath salts that have been demonstrated to display both effects. Further, the second part of my dissertation will continue examining the impacts of pre-exposure, this time with cocaine and MDMA. Cocaine and MDMA have commonly been reported in EDM scenes in which bath salt use occurs (voluntarily and inadvertently) and as been reported to be found in biological samples along with eutylone. Eutylone has been described as a hybrid compound in which it is primarily a reuptake inhibitor at the dopamine (DAT) and norepinephrine (NET) transporters but also acts as a substrate releaser at the serotonin transporter (SERT). Given its partial commonalities with the mechanisms of cocaine and MDMA, it is expected that prior exposure to either compound will attenuate the aversive effects of eutylone.