Neuroscience, Addictive Behavior and Novelty Seeking
PhD, Toxicology and Neuroscience, University of Texas, 2004
MS, Texas Tech University, 1998
BA, Baylor University, 1994
Drugs of abuse can lead to long-term neuroadaptations that are thought to underlie addictive behavior. There is also evidence that excessive engagement in rewarding non-drug behaviors can lead to addictive behaviors in human populations (Leeman & Potenza, Psychopharmacology, 2012; Marks, British J Addiction, 1990; Grant et al., Am. J. Drug Alcohol Abuse, 2010). Functional imaging studies have shown parallel changes in dopamine signaling between human cocaine users and obese subjects (Wang et al., J Addict Disord 2004; Volkow et al., 1990, 1993, 1996), suggesting that neuroadaptations associated with excessive drug abuse may not be unique to drug exposure.
Research in the Olsen laboratory is aimed at understanding the relationship between drug (e.g. cocaine) and non-drug rewards (e.g. sucrose, novelty seeking) in the context of detrimental behavioral and neural adaptations using mice and rats as model organisms. Experiments to address this relationship use a variety of in vivo and in vitro techniques including intravenous drug self-administration, transgenic rat and mouse lines, immunohistochemistry, and slice electrophysiology.
Using TetTag mice (Reijmers et al. Science, 2007) to monitor cell activity in two discrete points in time
While mice are on doxycycline (dox) diet, neuronal activation (denoted by lightning bolt) leads to tetracycline transactivator protein (tTA) expression, but “tagging” does not occur due to dox blocking activation of the tetO promoter. When dox diet is removed (opening the time window for Tag), neuronal activation leads to expression of 1) tau-LacZ (Tag) and 2) tetracycline-insensitive tTA (tTAH100Y; tTA*, yellow) that initiates a feedback loop. Tag time window is closed by resuming dox diet, but the tTA* feedback loop maintains expression of LacZ that was induced while the window was open. Thus, Tag induced by a treatment while the window is open will be persistent and identifiable in the tissue. Tag window can be closed and resist tagging during a second treatment that occurs shortly before taking tissue. Neural activation associated with the second treatment can be identified using classical ieg immunohistochemistry. This approach allows distinct visualization of neuronal activation associated with only the first treatment (Beta-galactoside: the LacZ gene product), only the second treatment (Fos or another ieg), or both (dual labels). NeuN staining reveals neural nuclei. Bottom: Visualization of labeling of two different treatments in tissue from a TetTag mouse. Tissue from a wildtype (WT) littermate shows an expected absence of beta-galactosidase label.
Addiction is a chronically relapsing disorder that is strongly modulated by positive and negative environmental factors. Our lab focuses on how these environmental factors can influence drug intake and drug seeking using rat and mouse models of addiction.
We have two major projects to investigate the environmental factors and addiction:
- Environmental modulation of drug seeking ensembles. Transgenic approaches are used to identify and manipulate cells that are engaged during drug seeking following intravenous drug self-administration. We are studying the effects of positive and negative environmental factors on drug seeking and the activity of cells within drug seeking ensembles.
- The impact of mild traumatic brain injury (mTBI) on addiction and mesocorticolimbic function. This work is done in collaboration with Drs. Brain Stemper and Matthew Budde in the Department of Neurosurgery. We are examining the effects of mTBI on drug self-administration, drug seeking, and mesocorticolimbic function using diffusion tensor imaging (DTI) and functional connectivity.
(Muelbl MJ, Slaker ML, Shah AS, Nawarawong NN, Gerndt CH, Budde MD, Stemper BD, Olsen CM.) Sci Rep. 2018 Jul 02;8(1):9941.
(Nelson LD, Furger RE, Ranson J, Tarima S, Hammeke TA, Randolph C, Barr WB, Guskiewicz K, Olsen CM, Lerner EB, McCrea MA.) J Neurotrauma. 2018 Jan 15;35(2):249-259.
(Olsen CM, Liu QS.) Front Biol (Beijing). 2016 Oct;11(5):376-386.
(LD Nelson, RE Furger, J Ranson, S Tarima, TA Hammeke, C Randolph, WB Barr, K Guskiewicz, CM Olsen, EB Lerner, and MA McCrea.) Journal of Neurotrauma. (in press).
(Stemper B.D., Shah A.S., Budde M.D., Chiariello R., Wilkins N., Olsen C., Mehta P., Kurpad S.N., McCrea M., Pintar F.A. .) 2015 IRCOBI Conference Proceedings. 198-207.
(Helfand AI, Olsen CM, Hillard CJ.) Int J Mol Sci. 2017 Jul 27;18(8).
(Stemper BD, Shah AS, Chiariello R, Olsen CM, Budde MD, Glavaski-Joksimovic A, McCrea M, Kurpad SN, Pintar FA.) Ann Biomed Eng. 2016 Nov;44(11):3252-3265.
(Muelbl MJ, Nawarawong NN, Clancy PT, Nettesheim CE, Lim YW, Olsen CM.) Psychopharmacology (Berl). 2016 07;233(14):2799-811.
(Stemper, BD, AS Shah, R Chiariello, CM Olsen, MD Budde, A Glavaski-Joksimovic, M McCrea, SN Kurpad, FA Pintar .) Annals of Biomedical Engineering. .
(Muelbl, MJ, NN Nawarawong, PT Clancy, CE Nettesheim, YW Lim, CM Olsen .) Psychopharmacology. .
(Stemper BD, Shah AS, Budde MD, Olsen CM, Glavaski-Joksimovic A, Kurpad SN, McCrea M, Pintar FA.) Front Neurol. 2016;7:31.
(Zhong L, Brown J, Kramer A, Kaleka K, Petersen A, Krueger JN, Florence M, Muelbl MJ, Battle M, Murphy GG, Olsen CM, Gerges NZ.) J Neurosci. 2015 May 13;35(19):7503-8.