Graduate Studies Faculty
Gregory P. Mark, Ph.D.
Research Interests:Acetylcholine, Animal models of addiction, Dopamine, Neurochemistry, Behavioral pharmacology » PubMed Listing
Preceptor RotationsAcademic Term Available Summer 2016 No Fall 2016 No Winter 2016 No Spring 2016 No Summer 2017 No Fall 2017 No Winter 2017 No Spring 2017 No
Faculty MentorshipDr. Mark is not available as a mentor for 2016-2017.
- Neurophysiology/neurochemistry of motivation and reward
- drug addiction
Summary of Current Research
The research in my laboratory is broadly concerned with exploring the biological bases of motivation, reward, and behavior reinforcement. Much of this effort is centered on understanding the neurochemical substrates that mediate drug reward and ultimately addiction. One important neural pathway underlying these behaviors originates in the area of the ventral midbrain and sends connections to a variety of higher brain structures including the nucleus accumbens, prefrontal cortex, neostriatum, and amygdala. The projections of this pathway communicate with other brain sites using a variety of neurotransmitter systems including dopamine, acetylcholine, GABA, and glutamate. We are interested in determining the neurochemical changes that occur during long-term methamphetamine and cocaine exposure and to what extent each of the neurotransmitters affect drug-seeking behavior.
My research relies on several methodological strategies including neurochemical, behavioral, electrophysiological, and biochemical techniques that are used to investigate the role of the nucleus accumbens, ventral tegmental area, and other limbic structures in the development of conditioned behavior and drug-seeking. In one line of experiments, we use in vivo microdialysis to monitor the release of neurotransmitters in freely-behaving rats during the presentation of primary and secondary rewards. The goal is to determine which alterations in neurotransmitter systems correlate with changes in reward value of drugs and stimuli that are associated with drugs. Behavioral pharmacology techniques are used to study the impact of receptor specific agonists and antagonists on drug self-administration behavior.
Repeated exposure to drugs such as cocaine and methamphetamine can cause long-term (perhaps permanent) changes in neuronal firing patterns and neurotransmitter output (release), receptor density or effector coupling, signal transduction mechanisms, and gene expression. Through collaborative efforts with other OHSU researchers, we have studied the impact of active (i.e. self-administered) and passive (i.e. response independent) drug exposure on neuronal plasticity and biochemical markers associated with these processes. In several instances, we have found that active drug-seeking causes changes in neurotransmitter levels, neuron firing, and gene expression patterns that are distinctly different from those induced strictly through pharmacological intervention. Identifying and understanding such changes is a critical step toward determining the neural basis of addictive behavior and developing strategies to combat addiction.
Dobbs, LK & Mark, GP (2008) Comparison of systemic and local methamphetamine treatment on acetylcholine and dopamine levels in the ventral tegmental area in the mouse. Neuroscience, 156(3): 700-711.
Jaworski, JJ, Hansen, ST, Kuhar, MJ & Mark, GP (2008) Injection of CART (Cocaine- and Amphetamine- Regulated Transcript) peptide into the nucleus accumbens inhibits cocaine self-administration in rats. Behavioral Brain Research, 191: 266-271.
Hansen ST, Mark GP (2007) The nicotinic acetylcholine receptor antagonist mecamylamine prevents escalation of cocaine self-administration in rats with extended daily access.Psychopharmacology,194:53-61.
Mark GP, Kinney AE, Zhu X, Finn DA, Berger SP, Mader, SL, Bechtholt AJ (2006) Injection of oxotremorine in nucleus accumbens shell reduces cocaine but not food self-administration in rats. Brain Research, 1123 (1): 51-59.
DuMont EC, Mark GP, Mader S, Williams JT (2005) Self-administration enhances excitatory synaptic transmission in the bed nucleus of the stria terminalis. Nature Neuroscience. 8(4):413-4.
Mitchell JM, Cunningham CL, Mark GP (2005) Locomotor activity predicts acquisition of self-administration behavior but not cocaine intake. Behavioral Neuroscience. 119(2):464-472.
- PhD (1988) University of Delaware, Newark
- Research Staff Member/Lecturer, Department of Psychology, Princeton University
- NIH Postdoctoral Fellow, Department of Psychology, Princeton University