Christopher M. Olsen, PhD
Phone: 414 955-7629
BA - Baylor University, Waco, TX - 1994
MS - Texas Tech University, Lubbock, TX - 1998
PhD - Toxicology and Neuroscience, University of TX, Austin - 2004
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.
Olsen, CM (2011) Natural rewards, neuroplasticity, and non-drug addictions. Neuropharmacology. 61: 1109-22.
Olsen, CM, DS Childs, GD Stanwood, and DG Winder (2010) Operant sensation seeking requires metabotropic glutamate receptor 5 (mGluR5). PLoS ONE. 5(11): e15085. doi:10.1371
Olsen, C Mand DG Winder (2009) Operant sensation seeking engages similar neural substrates to operant drug seeking in C57 mice. Neuropsychopharmacology 34:1685-94.
Schramm-Sapyta, NL, CM Olsen, and DG Winder (2006) Cocaine self-administration reduces excitatory responses in mouse nucleus accumbens shell. Neuropsychopharmacology 31:1444-51.
Olsen, C Mand CL Duvauchelle (2006) Prefrontal cortex D1 modulation of the reinforcing properties of cocaine. Brain Research 1075: 299-35.