Faculty and Staff
Pavel I. Ortinski, Ph.D.
|Title:||Assistant Professor of Pharmacology, Physiology & Neuroscience
|Department:||Pharmacology, Physiology & Neuroscience
School of Medicine
Pharmacology, Physiology & Neuro
The Children's Hospital of Philadelphia, University of Pennsylvania
Our lab investigates neuronal plasticity that underlies behavioral changes associated with drug addiction. We use cocaine self-administration in the rat as an animal model of cocaine use disorder. This model may be used to approximate several prominent features of human cocaine use, including escalation of drug intake and relapse after drug withdrawal. We are interested in understanding how these behavioral changes are encoded at the neuronal activity level. Our previous research has shown that the strength of excitatory synaptic signaling in the nucleus accumbens depends on duration of withdrawal from cocaine and availability of endogenous cannabinoids. We have also demonstrated that cocaine self-administration increases signaling at extrasynaptic NMDA receptors, excitatory ion channels sensitive to glutamate release from astroglia. We are currently exploring how glutamate and other neuromodulators released from astroglial cells regulate activity of single neurons and neuronal networks. For this research, we make extensive use of single-cell electrophysiology, stereotaxic injections of viral tracers and reporters, and Ca2+ imaging techniques.
Although our main focus is on drug use disorders, we are broadly interested in neuronal correlates of behavior. Over the years, we have collaborated with different groups studying neuronal control of food intake, excitatory/inhibitory balance in schizophrenia, and, most recently, neuronal plasticity in HIV associated neurological disorders.
- Ortinski P.I., Vassoler F.M., Carlson G.C., and Pierce R.C.: Temporally dependent changes in cocaine-induced synaptic plasticity in the nucleus accumbens shell are reversed by D1-like dopamine receptor stimulation. Neuropsychopharmacology, 2012, 37:1671-82.
- Gandal, M.J., Sisti, J., Klook, K., Ortinski, P.I., Leitman, V., Liang, Y., Thieu, T., Pierce, R.C., Jonak, G., Gur R.E., Carlson, G., Siegel, S.J.: GABA(B)-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction. Translational Psychiatry, 2012, 2, e142, doi:10.1038/tp.2012.69.
- Ortinski, P.I., Turner, JR., Pierce R.C. Extrasynaptic targeting of NMDA receptors following D1 dopamine receptor activation and cocaine self-administration. Journal of Neuroscience, 2013, 33:9451-61
- Mietlicki-Baase, E.G., Ortinski, P.I., Rupprecht, L.E., Olivos, D.R., Alhadeff, A.L., Pierce, R.C., Hayes, M. The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors. Am J Physiol Endocrinol Metab, 2013, 305:E1367-74.
- Zhou L., Andersen H., Arreola A.C., Turner J.R., Ortinski P.I. Behavioral history of withdrawal influences regulation of cocaine seeking by glutamate re-uptake. PLoS One, 2016, 11:e0163784.
- Zhou L., Fisher M.L., Cole R.D., Gould T.J., Parikh V., Ortinski P.I., Turner J.R. Neuregulin 3 signaling mediates nicotine-dependent synaptic plasticity in the orbitofrontal cortex and cognition. Neuropsychopharmacology, 2017 [epub ahead of print]. doi: 10.1038/npp.2017.278.
- Hernandez N.S., O'Donovan B., Ortinski P.I., Schmidt H.D. Activation of glucagon-like peptide-1 receptors in the nucleus accumbens attenuates cocaine seeking in rats. Addiction Biology, 2017 [epub ahead of print]. doi: 10.1111/adb.12583.
Fundamental Neuroscience I and II, Medical Neuroanatomy, Medical Neuropharmacology, Seminar on Manuscript Writing