Our research examines the neurobiological mechanisms of reinforcement learning and motivational control and seeks to identify how these mechanisms are altered in psychiatric illnesses, such as substance abuse. In this work, we use an integrative methodological approach that incorporates in vivo electrochemistry (fast scan cyclic voltammetry), in vivo optogenetics and preclinical behavioral analyses. We are currently investigating the neurobiological processes that underlie the ability of reward-associated cues to modulate ongoing behavior. Our recent findings show that midbrain cholinergic mechanisms powerfully regulate cue-induced cocaine-seeking behavior and suggest that cholinergic receptor modulation of phasic dopamine signaling may be critical for this behavior. Through ongoing projects, we are continuing to examine the role of cholinergic and dopaminergic mechanisms in cue-induced drug-seeking. In other work, we are investigating phasic dopamine mechanisms in nicotine addiction and the potential ability of tobacco product additives to enhance nicotine reinforcement through the regulation of dopamine signaling. In addition to our drug addiction research, we are also determining the role of cholinergic and dopaminergic mechanisms in other psychiatric illnesses, such as major depressive disorder (MDD). The goals of our research are to provide new insight into the mechanistic basis of these complex behaviors and to identify novel therapeutic targets to treat psychiatric disorders.
- Solecki W, Wickham R, Behrens S, Wang J, Zwerling B, Mason G, Addy NA (2013). Differential role of ventral tegmental area acetylcholine and N-Methyl-D-Aspartate receptors in cocaine-seeking. Neuropharmacology. In press.
- Wickham RJ, Solecki W, Rathbun LR, McIntosh JM and Addy NA. (2013) Ventral tegmental area alpha6beta2 nicotinic acetylcholine receptors modulate phasic dopamine release in the nucleus accumbens core. Psychopharmacology. Apr 30 Epub.
- Wickham RJ, Solecki W, Rathbun LR, Neugebauer NM, Wightman RM and Addy NA. (2013) Advances in studying phasic dopamine signaling in brain reward mechanisms. Frontiers in Bioscience. E5, 982-999, June 1. Review.
- Addy NA, Daberkow DP, Ford JN, Garris PA and Wightman RM. (2010) Sensitization of rapid dopamine signaling in the nucleus accumbens core and shell after repeated cocaine in rats. Journal of Neurophysiology. 104(2): 922-31
- Addy NA, Fornasiero EF, Stevens TR, Taylor JR, Picciotto MR. (2007) Role of calcineurin in nicotine-mediated locomotor sensitization. Journal of Neuroscience. 27(32): 8751-8580.