Emotion has a profound impact on animal behavior. In fact, the same neural mechanisms of learning that evolved to guide animals toward natural rewards also regulate mood. The goal of my research program is to understand the neural regulation of emotion, or affect, and the control it exerts over adaptive and, in the case of obesity and drug-seeking, maladaptive behavior.
To that end, I examine the role of brain nuclei in hedonic and motivational processing by recording changes in neuronal cell firing rates. These studies have revealed that patterned firing rate changes of nucleus accumbens neurons reflect the devaluation of a natural reward as it comes to predict, and is devalued by, future cocaine availability. I also use fast-scan cyclic voltammetry to examine dopamine transmission in this brain region. Dopamine release can be seen in response to a sweet taste that increases the firing rate of dopamine neurons. However, when this sweet taste is devalued by cocaine availability, dopamine concentration is transiently reduced. The dynamic nature of this conditioned switch in affect and the neural code reveals a mechanism by which cues may induce negative affect and subsequent drug-seeking behavior.
- Wheeler, D.S., Robble, M.A., Hebron, E.M., Dupont, M.J. Ebben, A.L., Wheeler, R.A. Drug-predictive cues activate aversion-sensitive striatal neurons that encode drug seeking. The Journal of Neuroscience. 2015. May 6; 35 (18):7215-7225. PMID: 25948270.
- Twining, R.C., Wheeler, D.S., Ebben, A.L., Jacobsen, A.J., Robble, M.A., Mantsch, J.R., Wheeler, R.A. Aversive stimuli drive drug seeking in a state of low dopamine tone. Biological Psychiatry. 2015. May 15; 77 (10):895-902. PMID: 25442790
- Freet, CS, Wheeler, RA, Leuenberger, E, Mosbleck, NA, Grigson, PS. Fischer rats are more sensitive than Lewis rats to the suppressive effects of morphine and the aversive kappa-opioid agonist spiradoline. Behavioral Neuroscience. 2013. Oct; 127 (5):763-70. PMID: 24128363
- Graf, E.N., Wheeler, R.A., Baker, D.A., Ebben, A.L., McReynolds, J.R., Robble, M.A., Vranjkovic, O., Wheeler, D.S., Mantsch, J.R., and Gasser, P.J. Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and potentiate reinstatement of cocaine seeking. 2013. The Journal of Neuroscience. 2013. 29, 11800-11810. PMID: 23864669
- Park, J., Wheeler, R.A., Fontillas, K., Keithley, R.B., Carelli, R.M., Wightman, R.M. Catecholamines in the bed nucleus of the stria terminalis reciprocally respond to reward and aversion. Biological Psychiatry. 2012. Feb. 15;71(4):327-334. PMID: 22115620
- Wheeler, R.A., Aragona, B.J., Fuhrmann, K.A., Day, J.J, Jones, J.L., Wightman, R.M., Carelli, R.M. Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state. Biological Psychiatry. 2011. Jun 1;69(11):1067-74. PMID: 21481843
- Grigson, P.S., Twining, R.C., Freet, C.S., Wheeler, R.A., & Geddes, R.I. Drug-induced suppression of CS intake: Reward, aversion, and addiction. 2009. In: Conditioned Taste Aversion: Behavioral and Neural Processes, S. Reilly & T. Schachtman, Editors. Oxford University Press. NY, NY.
- Jones, J.L., Day J.J., Aragona B.J., Wheeler R.A., Wightman R.M., Carelli R.M. Basolateral Amygdala Modulates Terminal Dopamine Release in the Nucleus Accumbens and Conditioned Responding. Biological Psychiatry. 2009 Dec 29. PMID: 20044074
- Wheeler, R.A., Carelli, R.M. Dissecting motivational circuitry to understand substance abuse. Neuropharmacology. 2009. 56 Suppl 1:149-59. PMID: 18625253
- Roitman, M.F., Wheeler R.A., Wightman R.M., Carelli R.M. Real-time chemical responses in the nucleus accumbens differentiate rewarding and aversive stimuli. Nature Neuroscience. 2008 Dec;11(12):1376-7. PMID: 18978779
- Wheeler, R.A., Twining, R.C., Jones, J.L., Slater, J.M., Grigson, P.S., Carelli, R.M. Behavioral and electrophysiological indices of negative affect predict cocaine self-administration. Neuron. 2008 Mar13;57(5) 774-85. PMID: 18341996
- Jones, JL, Wheeler, RA, Carelli, RM. Behavioral and neural responding is unaltered following periods of abstinence from sucrose. Synapse. 2007 Mar;62(3):219-28. PMID: 18088061
- Wheeler, RA, Carelli RM. The neuroscience of pleasure: Focus on Ventral pallidum firing codes hedonic reward: when a bad taste turns good. J Neurophysiol. 2006 Aug 2. PMID: 16885518
- Wheeler, RA, Roitman, MF, Grigson, PS, Carelli, RM. Single neurons in the nucleus accumbens track relative reward. International Journal of Comparative Psychology. 2005 18; 320-332.
- Roitman MF, Wheeler RA, Carelli RM. Nucleus accumbens neurons are innately tuned for rewarding and aversive taste stimuli, encode their predictors, and are linked to motor output. Neuron. 2005 Feb 17;45(4):587-97. PMID: 15721244