Assistant Research Scientist

The translational research that I conduct rests at the intersection of psychology, pharmacology, and genetics. My work is focused on understanding the neural mechanisms responsible for decision-making and impulsivity in relation to drug and alcohol abuse, and on developing novel treatment strategies for these disorders. Our group uses a combination of behavioral pharmacology, genetics, electrophysiology, and fMRI to conduct research in both animal and human models of choice. By integrating the pharmacological and genetic results of animal studies with human traits such as impulsivity, time perspective, and delay-discounting, it becomes possible to determine potential mechanisms by which motivation and preference can be altered.

For example, we have recently shown that there is robust individual variability in an animal model of preference and aversion following administration of the non-specific opioid antagonist naltrexone. Our evidence suggests that this variability may result from differences in distribution and/or function of mu opioid receptors within key regions of the CNS reward pathway. We have obtained similar results in a human model of alcohol self-administration and have successfully correlated naltrexone-induced aversion with baseline ethanol consumption in both species. We have also been able to show that the endogenous opioid system contributes to performance on a delay-discounting task in humans and that this performance can be altered by single administration of naltrexone. We are now looking at differences in the BOLD signal in human alcoholics following naltrexone administration and comparing this to the activity we see in healthy controls. Together, these results indicate a mechanism by which endogenous opioid are affecting decision-making and preference and may point the way towards novel therapeutic targets for drug and alcohol addiction.

Recent Publications:

Margolis EB, Mitchell JM, Ishikawa J, Hjelmstad GO, Fields HL. Midbrain dopamine neurons: projection target determines action potential duration and dopamine D(2) receptor inhibition.  J Neurosci. 28(36):8908-13, 2008.

Mitchell JM, VC Tavares, HL Fields, M D’Esposito, CA Boettiger (2007) Regulation of Impulsivity by Endogenous Opioids in Alcoholics and Healthy Controls, Neuropsychopharmacology, 32(2): 439-449.

Mitchell JM, Fields HL, White RL, Meadoff TM, Joslyn G, Rowbotham MD (2007) The ASP-40 mu opioid receptor allele does not predict naltrexone treatment efficacy in heavy drinkers. J Clin Psychopharmacol, 27(1): 112-114.

Mitchell, JM, LJ Bergren, KS Chen, HL Fields (2006) Cholecystokinin is necessary for the expression of morphine conditioned place preference, Pharmacology, Biochemistry, and Behavior, 85(4): 787-795.

Mitchell, JM, HL Fields, M D’Esposito, CA Boettiger (2005) Impulsive responding in alcoholics. Alcoholism: Clinical and Experimental Research, 29(12): 2158-2169.

Mitchell, JM, MT Liang, & HL Fields (2005) A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats. Psychopharmacology, 182(3): 384-392.

Mitchell, JM, CL Cunningham, GP Mark (2005) Locomotor activity predicts acquisition of self-administration behavior but not cocaine intake. Behavioral Neuroscience, 119(2): 464-72.

Paladini, CA, JM Mitchell, GP Mark, & JT Williams (2004) Cocaine self-administration specifically decreases alpha-adrenoreceptor regulation of mGluR-mediated inhibition in dopamine neurons. Journal of Neuroscience, 24: 5209 – 5215.

Valverde O, T Mantamadiotis, M Torrecilla, L Ugedo, J Pineda, S Bleckmann, P Gass, O Kretz, JM Mitchell, G Schütz and R Maldonado (2004) Modulation of Anxiety-Like Behavior and Morphine Dependence in CREB-Deficient Mice. Neuropsychopharmacology, 29(6): 1122-1133.

Valjent, E, JM Mitchell, MJ Besson, J Caboche, & R Maldonado (2002) Behavioural and biochemical evidence for interactions between Delta9-tetrahydrocannabinol and nicotine. British Journal of Pharmacology, 135 (2): 564-78.

Mitchell, JM, AI Basbaum, & HL Fields (2000) A locus and mechanism of action for associative morphine tolerance. Nature Neuroscience, 3 (1): 47-53.