John R. Mantsch, Ph.D. Research Lab
Understanding of the neurobiological basis of CNS disease to develop new and more effective treatment strategies.
The primary objective of my research program is to use our understanding of the neurobiological basis of CNS disease to develop new and more effective treatment strategies. Current research in my laboratory focuses on exploring the relationship between stress and drug addiction, identifying the neurobiological mechanisms underlying drug craving and relapse, and developing new medications for the management of addiction and other neuropsychiatric conditions. Specific projects include the study of addiction-related glucocorticoid-dependent neuroplasticity in stress and reward systems, determination of the role of CRF, noradrenergic, and dopaminergic signaling in stress-induced relapse, examination of the impact of chronic stress on addiction and depression. My laboratory uses a diverse range of behavioral, neurochemical, and cellular/molecular approaches and collaborates with a number of researchers at Marquette and other institutions. Research opportunities are available for post-docs and graduate and undergraduate students.
My laboratory is also involved in drug development activities in collaboration with the Baker lab at Marquette University and through agreements with Promentis Pharmaceuticals, a company that I co-founded along with Dr. Baker. (Promentis Pharmaceuticals, Inc.). Funding for my research is provided by the National Institute on Drug Abuse and the Charles E. Kubly Mental Health Research Center.
Current Graduate Students: Elizabeth Doncheck
Past Graduate Students: Dr. Evan Graf; Dr. Jordan Blacktop; Dr. Oliver Vranjkovic
Current Post-Docs: Dr. Jayme McReynolds
Past Post-Docs: Dr. Yazmin Guzman-Mueller, Dr. Robert Twining; Dr. David Pena
Research Technicians: Nick Raddatz; Erik Van Newenhizen; Luke Urbanik; Jacob Mathy
McReynolds, J.R., Doncheck, E.M., Li, Y., Vranjkovic, O., Graf, E.N., Ogasawara, D., Cravatt, B.F., Baker, D.A., Liu, Q.-S., Hillard, C.J., Mantsch, J.R. (2017) Stress promotes drug seeking through glucocorticoid-dependent endocannabinoid mobilization in prelimbic cortex. Biological Psychiatry. doi: http://dx.doi.org/10.1016/j.biopsych.2017.09.024
Doncheck, E.M., Urbanik, L.A., DeBaker, M.C., Barron, L.M., Liddiard, G.T., Tuscher, J.J., Frick, K.M., Hillard, C.J., Mantsch, J.R. (2017) 17β-estradiol potentiates the reinstatement of cocaine seeking in female rats: role of the prelimbic prefrontal cortex and cannabinoid type-1 receptors. Neuropsychopharmacology. doi: 10.1038/npp.2017.170.
McReynolds, J.R., Taylor, A., Ambrosius, T., Derricks, O., Vranjkovic, O., Baker, D.A., Wheeler, R.A., Gasser, P.J., Mantsch, J.R. (2017) Corticosterone potentiation of cocaine-induced reinstatement of conditioned place preference in mice is mediated by blockade of the organic cation transporter 3. Neuropsychopharmacology 42:757-765.
Mantsch, J.R., Baker, D.A., Funk, D., Le, A., Shaham, Y. (2016) Stress-induced reinstatement of drug seeking: 20 years of progress. Neuropsychopharmacology Reviews 41:335-56.
Blacktop, J.M., Vranjkovic, O., Mayer, M., Van Hoof, M., Baker, D.A., Mantsch, J.R. (2016) Antagonism of GABA-B but not GABA-A receptors in the VTA prevents stress- and intra-VTA CRF-induced reinstatement of extinguished cocaine seeking in rats. Neuropharmacology 102:197-206.
McReynolds, J.R., Doncheck, E.M., Vranjkovic, O., Ganzman, G.S., Baker, D.A., Hillard, C.J., Mantsch, J.R. (2016) CB1 receptor antagonism blocks stress-potentiated reinstatement of cocaine seeking in rats. Psychopharmacology 233:99-109.
Twining, R.C., Daniel S Wheeler, D.S., Ebben, A.L., Jacobsen, A.J., Robble, M.A., Mantsch, J.R., Wheeler, R.A. (2015) Aversive stimuli drive drug seeking in a state of low dopamine tone. Biological Psychiatry 77:895-902.
Vranjkovic, O., Gasser, P.J, Gerndt, C., Baker, D.A., Mantsch, J.R. (2014) Stress-induced cocaine seeking requires a beta-2 adrenergic receptor-regulated pathway from the ventral bed nucleus of the stria terminalis that regulates CRF actions in the ventral tegmental area. Journal of Neuroscience 34:12504-14.
McReynolds, J.R., Vranjkovic, O., Thao, M., Baker, D.A., Makky, K., Lim, Y., Mantsch, J.R. (2014) Beta-2 adrenergic receptors mediate stress-evoked reinstatement of cocaine-induced conditioned place preference and increases in CRF mRNA in the bed nucleus of the stria terminalis in mice. Psychopharmacology. 231:3953-63.
Graf, E.N., Wheeler, R.A., Baker, D.A., Ebben, A.L., Hill, J.E., McReynolds, J.R., Robble, M.A., Vranjkovic, O., Wheeler, D.S., Mantsch, J.R.*, Gasser, P.J.* (2013) Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and potentiate reinstatement of cocaine seeking. Journal of Neuroscience 33:11800-10. *Equal contribution
Vranjkovic, O., Hang, S., Baker, D.A., Mantsch, J.R. (2012) Beta adrenergic receptor mediation of stress-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: roles for beta-1 and beta-2 adrenergic receptors. Journal Pharmacology Experimental Therapeutics 342:541-51.
Blacktop, J., Seubert, C., Baker, D.A., Ferda, N., Lee, G., Graf, E.N., Mantsch, J.R. (2011) Augmented cocaine seeking in response to stress or CRF delivered into the ventral tegmental area following long-access self-administration is mediated by CRF receptor type 1 but not CRF receptor type 2. Journal of Neuroscience 31: 11396-403.
Graf, E.N., Hoks, M.A., Baumgardner, J. Sierra, J., Vranjkovic, O., Bohr, C., Baker, Mantsch, J.R. (2011) Adrenal activity during repeated long-access cocaine self-administration is required for later icv CRF-induced and CRF-dependent stressor-induced reinstatement in rats. Neuropsychopharmacology 36: 1444-1454.
Figueroa-Guzman, Y., Mueller, C., Vranjkovic, O., Wisniewski, S., Yang, Z., Li, S.J., Graf, E.N., Baker, D.A., Mantsch, J.R. (2011) Oral administration of levo-tetrahydropalmatine attenuates reinstatement of extinguished cocaine seeking by cocaine, stress or drug-associated cues in rats. Drug and Alcohol Dependence 116: 72-79.
Mantsch, J.R., Weyer, A., Vranjkovic, O., Baker, D.A., Beyer, C.E., Caretta, H. (2010) Involvement of noradrenergic neurotransmission in the stress- but not cocaine-induced reinstatement of extinguished cocaine-induced conditioned place preference in mice: Role for beta-2 adrenergic receptors. Neuropsychopharmacology 35:2165-78.