Assistant Professor, School of Medicine 

Affiliated Faculty Neuroscience

John Muschamp.jpeg

john.muschamp@temple.edu 849 MERB 3500 N Broad St Philadelphia PA 19122

Dr. Muschamp’s laboratory studies the neurobiology of motivation, affect, and executive function and how they are altered in psychiatric disorders like drug addiction. To model these psychological constructs in animals we use a number of behavioral paradigms like intracranial self-stimulation (ICSS), place conditioning (CPP), and the 5-choice serial reaction time task (5CSRTT). To understand part of the neurocircuitry that is common to these different behaviors (i.e. the mesolimbic dopamine pathway), we have used in vivo microdialysis, electrophysiology, viral-mediated gene transfer, and a variety of neuroanatomical techniques. Important modulators of mesolimbic dopamine transmission are hypocretin (orexin) and dynorphin peptides released by projections from the hypothalamus. We have demonstrated that the hypocretin system is an essential integrator of reward-relevant information that potently excites the midbrain dopamine reward pathway.

We have also shown that attenuated hypocretin signaling decreases the reinforcing effects of cocaine, rewarding lateral hypothalamic electrical stimulation, and natural rewards like sex behavior. Additionally, we have also established that decreased hypocretin transmission attenuates spontaneous- and cocaine-induced impulsive behavior. These effects appear to arise from the ability of hypocretin to modulate the aversive or depressive-like effects of hypocretin’s cotransmitter dynorphin. Understanding the relationship and interactions between hypocretin and dynorphin is a major goal of our research. Because disturbances in mood, motivation, and executive function often accompany addiction and other psychiatric illnesses (e.g. bipolar disorder), and may be mediated by disrupted function of the hypocretin-dynorphin system, our work is designed to determine the utility of hypocretin receptor antagonists for the treatment of substance use disorders or other psychiatric illnesses characterized by high levels of impulsivity.