The goal of my research is to elucidate the molecular basis of behavior. I am interested in the mechanisms that mediate alcohol and nicotine addiction separately, and those that are involved in alcohol and nicotine co-addiction. Alcohol and nicotine are two commonly used drugs, and addiction to both drugs is very prevalent. Alcohol and nicotine addiction have overlapping molecular mechanisms, and identifying these mechanisms will enable us to understand why these drugs are co-abused and to identify new molecular targets for treatment. We use a wide range of molecular and behavioral tools including transgenic mouse models, viral genetic manipulations, pharmacological tools and behavioral assays in mouse models of drug addiction.
A major focus in the lab is the nicotinic acetylcholine receptors (nAChRs) and how different nicotinic receptor subtypes mediate aspects of co-addiction. These receptors are widely expressed ligand-gated ion channels that are primarily found on pre-synaptic terminals and on neuronal cell bodies, and thus are poised to modulate neurotransmission and regulate neural circuits. As such, nAChRs are implicated in alcohol and nicotine addiction, anxiety, depression and learning/memory. Our goal is to identify how different nAChR subtypes, and how regulation of nAChRs can affect neuronal activity, circuit function and behavior.
We currently have several projects that focus on nAChRs in addiction: 1) Cholinergic regulation of alcohol aversion. A major project in our lab is to determine how the nAChRs mediate alcohol reward, aversion and consumption. Our recent work has uncovered a novel role for the nAChRs in alcohol aversion, and our goal is to identify the neuronal circuit and nAChR subtype that is involved. 2) Sex dependent regulation of nAChR gene expression. We recently discovered that the alpha6 and beta3 nAChR subtype are regulated by protein kinase C epsilon and sex hormones, resulting in oppositional expression of addiction-related behaviors in male versus female mice. Our goal is to determine how molecular regulation of these nAChR genes differs between sexes. 3) Altered abuse liability of electronic cigarette liquids. We are actively investigating whether the abuse liability of electronic cigarette liquid refills differs from nicotine alone, and whether this is modulated by flavors.
Lab website: https://sites.google.com/umn.edu/amleelab/home
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Br J Pharmacol. 2023 Mar 16. doi: 10.1111/bph.16071. RGS6 negatively regulates inhibitory G protein signaling in VTA dopamine neurons and positively regulates binge-like alcohol consumption in mice.
- Moen JK, Lee AM. Sex differences in the nicotinic acetylcholine receptor system of rodents: Impacts on nicotine and alcoholr eward behaviors. Front Neurosci. 2021 Sep 21;15:745783.
- DeBaker MC, Marron Fernandez de Velasco E, McCall NM, Lee AM, Wickman K. Differential impact of inhibitory G-protein signaling pathways in ventral tegmental area dopamine neurons on behavioral sensitivity to cocaine and morphine. eNeuro. 2021 Mar 26; 8(2):ENEURO. 0081-21.
- Moen JK, DeBaker MC, Myjak JE, Wickman K, Lee AM. Bidirectional sex-dependent regulation of α6 and β3 nicotinic acetylcholine receptors by protein kinase Cε. Addict Biol. 2021 May;26(3):e12954.
- Wong AL, McElroy SM, Robinson JM, Mulloy SM, El Banna FK, Harris AC, LeSage MG, Lee AM. Flavor-specific enhancement of electronic cigarette liquid consumption and preference in mice. Drug Alcohol Depend. 2020 Jun 1;211:107995.
- Touchette JC, Moen JK, Robinson JM, Lee AM. Enhancement of alcohol aversion by the nicotinic acetylcholine receptor drug sazetidine-A. Addict Biol. 2020 Apr 24:e12908.
- DeBaker MC, Moen JK, Robinson JM, Wickman K, Lee AM. Unequal interactions between alcohol and nicotine co-consumption: suppression and enhancement of concurrent drug intake. Psychopharmacology (Berl). 2020 Apr;237(4):967-978.
- DeBaker MC, Robinson JM, Moen JK, Wickman K, Lee AM. Differential patterns of alcohol and nicotine intake: Combined alcohol and nicotine binge consumption behaviors in mice. Alcohol. 2019;85:57-64.
- Touchette JC, Maertens JJ, Mason MM, O'Rourke KY, Lee AM. The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice without affecting concurrent nicotine consumption. Neuropharmacology. 2018 May 1;133:63-74.
- Eum S, Schneiderhan ME, Brown JT, Lee AM, Bishop JR. Pharmacogenetic evaluation to assess breakthrough psychosis with aripiprazole long-acting injection: a case report. BMC Psychiatry. 2017 Jul 3;17(1):238.
- Touchette JC, Lee AM. Assessing alcohol and nicotine co-consumption in mice. Oncotarget. 2017;8:5684-5685.
- O'Rourke KY, Touchette JC, Hartell EC, Bade EJ, Lee AM. Voluntary co-consumption of alcohol and nicotine: Effects of abstinence, intermittency, and withdrawal in mice. Neuropharmacology. 2016;109:236-246.
- Eum S, Lee AM, Bishop JR. Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations. Dialogues Clin Neurosci. 2016;18:323-337.
- Lee AM, Wu D-F, Dadgar J, Wang D, McMahon T, Messing RO. Protein kinase C epsilon phosphorylates α4β2 nicotinic acetylcholine receptors and promotes recovery from desensitization. Br J Pharmacol. 2015;172:430-441.
- Lee AM, Zou ME, Lim JP, Stecher J, McMahon T, Messing RO. Deletion of Prkcz increases intermittent ethanol consumption in mice. Alcohol Clin Exp Res. 2014;38:170-8.
Current Graduate Students:
Margot DeBaker (Neuroscience, University of Minnesota)
Sarah Mulloy (Neuroscience, University of Minnesota).
Amelia Schneider (Neuroscience, University of Minnesota).
Janna Moen (Neuroscience, University of Minnesota)