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, and investigation of the potential utility of plant-derived tetrahydroprotoberberine compounds (e.g., levo-tetrahydropalmatine) and novel cysteine prodrugs for the treatment of addiction. My laboratory uses a diverse range of behavioral, neurochemical, and cellular/molecular approaches and involves collaboration 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 National Center for Complementary and Alternative Medicine.
Graduate Students: Jordan Blacktop, Evan Graf, Oliver Vranjkovic
Post-Doctoral Fellow: Yazmin Figueroa-Guzman
Research Technician: Chris Mueller
- Wang, J.B., Mantsch, J.R. (2012) Development of l-tetrahydropalmatine as a new medication for cocaine addiction. Future Medicinal Chemistry 4: 177-186.
- Vaughn, L.K., Mantsch, J.R., Vranjkovic, O., Stroh, G., LaCourt, M., Kreutter, M., Hillard, C.J. (2012) Cannabinoid receptor Involvement in stress-induced cocaine reinstatement: potential interaction with noradrenergic pathways. Neuroscience 204: 117-124.
- 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. J Neurosci 31: 11396-403.
- Ghasemzadeh, M.B., Vasudevan, P., Giles, C., Purgianto, A., Seubert, C., Mantsch, J.R. (2011) Glutamatergic plasticity in prefrontal cortex and ventral tegmental area following withdrawal from cocaine self-administration. Brain Research 1413: 60-71
- 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.
- Amen, S.L., Piacentine, L., Ahmad, M, Li, S.J., Mantsch, J.R., Risinger, R.C., Baker, D.A. (2011) Repeated N-acetylcysteine reduces cocaine seeking in rodents and craving in cocaine-dependent humans. Neuropsychopharmacology 36:871-78.
- 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.
- Mantsch, J.R., Wisniewski, S., Vranjkovic, O., Peters, C., Becker, A., Valentine, A., Li, S.J., Baker, D.A., Yang, Z. (2010) Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats. Pharmacol Biochem Behav 97:310-6.
- Madayag, A., Kau, K., Lobner, D., Mantsch, J.R., Baker, D.A. (2010) Drug-induced plasticity contributing to heightened relapse susceptibility: neurochemical changes & augmented reinstatement in high-intake rats. J Neurosci 30:210-7.
- Ghasemzadeh, B.G., Vasudevan, P., Mueller, C., Seubert, C., Mantsch, J.R. (2009) Neuroadaptations in the cellular and postsynaptic metabotropic glutamate receptor mGluR5 and Homer proteins following extinction of cocaine self-administration. Neuroscience Letters, 452, 167-171.
- Ghasemzadeh, B.G., Vasudevan, P., Mueller, C., Seubert, C., Mantsch, J.R. (2009) Region specific alterations in glutamate receptor expression and subcellular distribution following extinction of cocaine self-administration. Brain Research, 1267, 89-102
- Kau, K., Madayag, A., Mantsch, J.R., Grier, M.D., Abdulhameed, O., Baker, D.A. (2008) Blunted System xc- in the Nucleus Accumbens Promotes Cocaine-Induced Drug Seeking. Neuroscience, 155, 530-557
- Mantsch, J.R., Baker, D.A., Serge, J.P., Hoks, M.A., Francis, D.M., Katz, E.S. (2008) Surgical adrenalectomy with diurnal corticosterone replacement slows escalation and prevents the augmentation of cocaine-induced reinstatement in rats self-administering cocaine under long-access conditions. Neuropsychopharmacology, 33, 814-26.
- Mantsch, J.R., Baker, D.A., Francis, D.M., Katz, E.S., Hoks, M.A., Serge, J.P (2008) Stressor- and corticotropin releasing factor-induced reinstatement and active stress-related behavioral responses are augmented following long-access cocaine self-administration by rats. Psychopharmacology, 195, 591-603
- Madayag, A., Lobner, D., Kau, K., Mantsch, J.R., Abdulhameed, O., Hearing, M., Grier, M., Baker, D.A. (2007) Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine. J. Neuroscience 27, 13968-13976
- Mantsch, J.R., Taves, S., Khan, T., Katz, E.S., Sajan, T., Tang, L.C., Cullinan, W.E., Ziegler, D.R. (2007) Restraint-induced corticosterone secretion and hypothalamic CRH mRNA expression are augmented during acute withdrawal from chronic cocaine administration. Neuroscience Letters, 415, 269-73.
- Mantsch, J.R., Li, S.-J., Risinger, R., Awad, S., Katz, E., Baker, D., Yang, Z. (2007) Levo-tetrahydropalmatine attenuates cocaine self-administration and cocaine-induced reinstatement in rats. Psychopharmacology, 192: 581-91.
- Mantsch, J.R., Cullinan, W.E., Tang, L.C., Baker, D.A., Katz, E.S., Hoks, M.A., Ziegler, D.R. (2007) Daily cocaine self-administration under long-access conditions augments restraint-induced increases in plasma corticosterone and impairs glucocorticoid receptor-mediated negative feedback in rats. Brain Research, 1167, 101-111
- Mantsch, J.R., Katz, E.S. (2007) Elevated glucocorticoids are necessary but not sufficient for the escalation of cocaine self-administration by chronic electric footshock stress in rats. Neuropsychopharmacology, 32, 367-376.