Gregory P. Mark
Associate Professor, Behavioral Neuroscience, OHSU
e-mail: markg@ohsu.edu
Major Areas
Neurochemistry of addiction; neurobiology of motivation and reinforcement
Previous Positions
Assistant Professor, Behavioral Neuroscience, OHSU
Research Staff Member/Lecturer, Department of Psychology, Princeton University
NIH Postdoctoral Fellow, Department of Psychology, Princeton University
Education
BA (1980) University of Delaware, Newark
MA (1985) University of Delaware, Newark
PhD (1988) University of Delaware, Newark
Research Interests
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. We have focused our attention on a neural circuit that arises in the ventral midbrain and terminates in the nucleus accumbens, prefrontal cortex, neostriatum, and amygdala. The neurotransmitter systems we study include dopamine, acetylcholine, glutamate, and GABA. We are interested in determining the neurochemical changes that occur in this circuit during long-term psychostimulant exposure and to what extent certain neurotransmitter systems 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 several other limbic structures in the development of learned contingencies (conditioning) and drug-seeking behavior. The in vivo neurochemical technique of microdialysis to be used to monitor the release of neurotransmitters in freely-behaving rats during the presentation of primary and secondary reinforcers. The goal is to determine which alterations in limbic neurochemistry correlate with changes in reinforcement value of stimuli. The second line of experiments derives from the results of the neurochemical studies and involves the use of traditional operant behavior measures (e.g. lever-pressing for food or intravenous drugs) during local pharmacological manipulation of discrete nuclei within the limbic system. Of particular interest here is 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 neural firing patterns and neurotransmitter output, receptor density or effector coupling, signal transduction mechanisms, and gene expression. Through collaborative efforts with other OHSU researchers, we have studies the impact of active (i.e. self-administered) and passive (i.e. response independent) psychostimulant 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, cell firing, and gene expression patterns that are distinctly different from those induced pharmacologically. Identifying and understanding such changes is a critical step toward determining the neural basis of addictive behavior and developing strategies to combat addiction.
Selected Recent Publications
Ford CP, Mark GP, Williams JT (2006) Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target locations. Journal of Neuroscience. in press.
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.
Paladini CA, Mitchell JM, Williams JT, Mark GP (2004) Cocaine self-administration specifically decreases adrenoceptor regulation of mGluR-mediated inhibition in dopamine neurons. Journal of Neuroscience. 24:5209-15.
Bechtholt AJ, Mark GP (2002) Enhancement of cocaine-seeking behavior by repeated nicotine exposure in rats. Psychopharmacology. 162:178-185.
Mark G, Finn D (2002) The relationship between hippocampal ACh release and cholinergic convulsant sensitivity in Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant selected mouse lines. Alcoholism: Clinical and Experimental Research. 26:1141-52.
Grubb M, Finn D, Welch J, Mark G (2002) Self-administration versus non-contingent cocaine differentially alters locomotor response to microinjection in GABAA receptor agents into the VTA of rats. Brain Research. 952:44-51.
Mark G, Hajnal A, Kinney A, Keys A (1999) Self-administration of cocaine increases the release of ACh to a greater extent than response-independent cocaine in the nucleus accumbens of rats. Psychopharmacology. 143:47-53.
Mark GP, Kinney AE, Grubb MC, Keys AS (1999) Involvement of acetylcholine in the nucleus accumbens in cocaine reinforcement. Annals of the New York Academy of Sciences.877;792-795.
Keys AS, Mark GP (1998) Amphetamine differentially modulates acetylcholine release in nucleus accumbens via D1 and D2 receptors. Neuroscience. 86:521-531.
Mark GP, Schwartz DH, West HL, Hernandez L, Hoebel BG (1991) Application of microdialysis to the study of motivation and conditioning: Measurement of dopamine and serotonin in freely-behaving rats. In T.E. Robinson & J.B. Justice (Eds.) Microdialysis in the Neurosciences, Amsterdam: Elsevier, 369-385.