Dr. España's doctoral thesis at the University of Wisconsin focused on the behavioral and physiological functions of the hypocretins, particularly as they relate to arousal-related processes including sleep/wake behavior and stress. His postdoctoral research at the Harvard Institutes of Medicine focused on elucidating the afferent innervation of the hypocretin neurons with an emphasis on aminergic inputs. In this work, Dr. España showed that the hypocretin neurons receive input from regions that govern motivation, homeostatic drive, behavioral state and autonomic tone.
Dr. España later joined Wake Forest School of Medicine where he used behavioral and neurochemical approaches to demonstrate that the hypocretins regulate the reinforcing effects of cocaine via actions on the mesolimbic dopamine system. His current research at Drexel focuses on hypocretin, dopamine, and norepinephrine regulation of arousal-related processes including sleep/wake function, stress and drug reinforcement.
España's laboratory uses a multidisciplinary approach to investigate the involvement of hypocretins in reward and addiction processes. Techniques include:
- Electrophysiological recordings of sleep/wake behavior
- Fast scan cyclic voltammetry
- Circuit- and cell type-specific manipulations
- Fiber photometry
- DREADDs
- Optogenetics
- Self-administration of drugs of abuse
- Single and multi-unit recordings in behaving animals
Selected Grants Funded
2R01DA03190 - Hypocretin/Orexin Regulation of Dopamine and Cocaine Reinforcement. This project investigates how hypocretin/orexin receptor blockade influences dopamine transmission and cocaine seeking.
R21DA057054 - Selective real-time activation of ERK1/2 signaling in dopamine neurons. Collaboration with Ole Mortensen. This project investigates to what extent disruption of ERK1/2 influences dopamine transmission and dopamine transporter expression.
UF1DA054817 - Preclinical Development of Novel Dual OXR/KOR Antagonists for Treatment of Substance Use Disorder. Collaboration with Hager Biosciences. This project will develop novel orexin kappa opioid receptor antagonists and test their effects of reducing intake, motivation, and seeking of cocaine, methamphetamine and fentanyl.
Commonwealth of PA CURE - Real-time ex vivo modulation of ERK1/2 signaling in dopamine neurotransmission. Collaboration with Wei Du. This project will use genetic tools to establish role of ERK1/2 in regulating dopamine proteins and signaling.
Completed
Commonwealth of PA CURE - Involvement of Hypocretin/Orexin in Opioid Withdrawal and Relapse. This project examines if treatment with the FDA approved dual hypocretin receptor 1 and receptor 2 antagonist Suvorexant (Belsomra®) during oxycodone abstinence reduces relapse to opioid use.
R21DA043787 - Pre-existing individual differences in dopamine uptake dynamics govern the motivation for cocaine. These studies examined the contribution of inherent, individual differences in dopamine neurotransmission to the subsequent risk and intensity of cocaine-associated behavior.
R01DA03190 - Hypocretin/Orexin Regulation of Dopamine and Cocaine Reinforcement. These studies used a combination of voltammetry, drug reinforcement, and virus-mediated gene manipulation techniques to examine the extent to which hypocretin signaling participates in the regulation of motivated behavior.
K01DA025279 - Hypocretin/Orexin Modulation of Reward and Addiction Processes. These studies utilize self-administration and microdialysis techniques in behaving rats, and voltammetry in anesthetized rats to examine whether the hypocretin system influences cocaine-self administration and whether these actions involved changes in the dopamine system.
NARSAD Award - Hypocretin regulation of dopamine neurotransmission. This study will use hypocretin knockout mice to examine the extent to which the hypocretin system is necessary for normal dopamine function under normal conditions and in response to stimulant drugs of abuse.