Laboratory of Neuropharmacology
Dr. Spigelman is a neuropharmacologist with research interests in translational neurobiology of neurodegenerative disorders, which includes studies on epilepsy, painful neuropathies, alcohol dependence, and radiation effects on brain function. For many years, his lab has studied alcohol-induced behavioral and physiological alterations in rodents and development of targeted treatments for alcoholism. They have also explored the mechanisms of inflammatory and neuropathic pain in studies that focused primarily on pathophysiological changes in transmitter release, and voltage- or ligand-gated ion channels in sensory neurons. These studies in turn revealed potential targets for development of novel analgesics such as peripherally-acting cannabinoid receptor ligands and gene therapy applications targeting select sodium channel subtypes which they are currently exploring.
Current Projects and Grants
R01 CA196263 (Schmidt/Spigelman MPI) 01/01/16 – 12/31/20
Peripherally-restricted cannabinoids for cancer and chemotherapy-induced pain,
This proposal focuses on establishing effectiveness and mechanisms of action of peripherally-restricted cannabinoids against: a) human oral carcinoma proliferation, b) oral carcinoma-induced pain, and c) chemotherapy-induced peripheral neuropathies (CIPNs).
R01 AA024527. (Spigelman) 09/01/16 – 08/31/20
Brain mechanisms of HPA axis dysregulation in alcohol dependence,
A combination of behavioral, electrophysiological, biochemical, and pharmacological techniques will be used to determine: 1) the role of glucocorticoids, 2) norepinephrine and 3) GABAergic neurotransmission in chronic alcohol-induced neuroadaptive changes in hypothalamic parvocellular neurosecretory cells; and 4) the role of the hypothalamic paraventricular nucleus in stress-induced increases in anxiety-like behavior and excessive alcohol intake in alcohol-dependence.
R01AA026530 (Fanselow/Spigelman MPI) 09/30/17 – 08/31/22
Heterogeneity in Stress Effects on Fear Learning, Ethanol Consumption and Anxiety
Focuses on a rat post-traumatic stress disorder model that exhibits high levels of voluntary alcohol consumption.
Migraine Research Foundation (Spigelman) 01/01/20 – 12/31/20
Stress- and Triptan-Induced Latent Sensitization: Neural Dynamics Underlying Migraine and Medication Overuse Headache.
Specific aims are designed to utilize behavioral, pharmacological, biochemical, and electrophysiological techniques to probe the mechanisms of latent sensitization and the mechanisms by which selective activation of peripheral cannabinoid receptors protects against the development of neural sensitization and chronic migraine.
T32 DA024635 (London) “Translational Neuroscience of Drug Abuse” 01/09/18 – 08/31/20
- Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation. Mulpuri Y, Marty VN, Munier JJ, Mackie K, Schmidt BL, Seltzman HH, Spigelman I. Neuropharmacology. 2018 Sep 1;139
- Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain. Seltzman HH, Shiner C, Hirt EE, Gilliam AF, Thomas BF, Maitra R, Snyder R, Black SL, Patel PR, Mulpuri Y, Spigelman I. J Med Chem. 2016 Aug 25;59(16):7525
- Radiation-induced alterations in synaptic neurotransmission of dentate granule cells depend on the dose and species of charged particles. Marty VN, Vlkolinsky R, Minassian N, Cohen T, Nelson GA, Spigelman I. Radiat Res. 2014 Dec;182(6):653-65. doi: 10.166
- Stress increases voluntary alcohol intake, but does not alter established drinking habits in a rat model of posttraumatic stress disorder. Meyer EM, Long V, Fanselow MS, Spigelman I. Alcohol Clin Exp Res. 2013 Apr;37(4):566-74. doi: 10.1111/acer.12012. Ep
- Mechanisms of reversible GABAA receptor plasticity after ethanol intoxication. Liang J, Suryanarayanan A, Abriam A, Snyder B, Olsen RW, Spigelman I. J Neurosci. 2007 Nov 7;27(45):12367-77.
List of collaborators within and outside of UCLA:
Cahill, C.M., Chiappelli, F., Fanselow, M.S., Faull, K.F., Herschman, H.R., Hokugo, A., Houser, C.R., Izquierdo, A., Jarrahy, R., Kim, Y., Kruger, L.,
Maidment, N.T., Marvizón, J.C.G., Messadi, D., Mito, R.S., Nishimura, I., Olsen, R.W., Schweizer, F.E., Scremin, O., Shao, X.M., Venugopal, S.,Wong, D
New York University: Schmidt, B.L.
University of Arizona: Vanderah, T.W.
University of Southern California: Damasio, A.
Binghamton University: Werner, DF
University of North Carolina, Chapel Hill: Morrow, A.L.
University of Texas, Dallas: Dussor, G
Tokushima University, Japan: Matsuka, Y.
List of Lab Members:
Vincent N. Marty, PhD, Senior Staff Researcher
Yatendra Mulpuri, BDS, PhD, Senior Postdoctoral Fellow
Toru Yamamoto, DDS, PhD, Postdoctoral Fellow
Joseph Munier, B.S., Ph.D. Graduate student, MCIP Graduate Program
Mikhail Izraylev, B.S., M.S. Graduate Student in Oral Biology
Qianyi (Ashley) Li, DDS, M.S. Graduate Student in Oral Biology
Our lab utilizes a variety of behavioral, electrophysiological, molecular biological, biochemical, and neuropharmacological techniques and can thus serve as an excellent facility for bench training of undergraduates, graduate students, and clinician-scientists.