My research goal is to improve preventive and treatment strategies for opioid misuse and use disorder by investigating involvement of thalamic voltage-gated (T-type) calcium channels in the morphine effects. My present work is focused on discovering changes in thalamocortical oscillations, sleep disturbances and thalamic excitability after repeated morphine administration. During PhD studies, I was determining the activity of alpha5 selective GABAA receptor modulators in animal models of schizophrenia. During Postdoctoral Fellowship, I established the importance of T-type calcium channels in thalamocortical oscillations that underlie clinically important effects of anesthesia.
Publications
Santrac A, Batinic B, Stamenic TT, Arandelovic J, Sharmin D, Knutson DE, Cook JM, Savic MM. Positive modulation of a5GABAA receptors leads to dichotomous effects in rats on memory pattern and GABRA5 expression in prefrontal cortex and hippocampus. Behav Brain Res. 2022 Jan 7;416:113578. PubMed PMID: 34508769
Timic Stamenic T, Manzella FM, Maksimovic S, Krishnan K, Covey DF, Jevtovic-Todorovic V, Todorovic SM. Further Evidence that Inhibition of Neuronal Voltage-Gated Calcium Channels Contributes to the Hypnotic Effect of Neurosteroid Analogue, 3ß-OH. Front Pharmacol. 2022;13:850658. PubMed PMID: 35677453
Timic Stamenic T, Todorovic SM. Thalamic T-Type Calcium Channels as Targets for Hypnotics and General Anesthetics. Int J Mol Sci. 2022 Feb 21;23(4). PubMed PMID: 35216466
Coulter I, Timic Stamenic T, Eggan P, Fine BR, Corrigan T, Covey DF, Yang L, Pan JQ, Todorovic SM. Different roles of T-type calcium channel isoforms in hypnosis induced by an endogenous neurosteroid epipregnanolone. Neuropharmacology. 2021 Oct 1;197:108739. PubMed PMID: 34339750
Timic Stamenic T, Feseha S, Manzella FM, Wallace D, Wilkey D, Corrigan T, Fiedler H, Doerr P, Krishnan K, Raol YH, Covey DF, Jevtovic-Todorovic V, Todorovic SM. The T-type calcium channel isoform Ca(v)3.1 is a target for the hypnotic effect of the anaesthetic neurosteroid (3ß,5ß,17ß)-3-hydroxyandrostane-17-carbonitrile. Br J Anaesth. 2021 Jan;126(1):245-255. PubMed PMID: 32859366
Timic Stamenic T, Feseha S, Manzella FM, Wallace D, Wilkey D, Corrigan T, Fiedler H, Doerr P, Krishnan K, Raol YH, Covey DF, Jevtovic-Todorovic V, Todorovic SM. The T-type calcium channel isoform Ca(v)3.1 is a target for the hypnotic effect of the anaesthetic neurosteroid (3ß,5ß,17ß)-3-hydroxyandrostane-17-carbonitrile. Br J Anaesth. 2020 Aug 25. [Epub ahead of print] PubMed PMID: 32859366
Simon Feseha, Tamara Timic Stamenic, Damon Wallace, Caesare Tamag, Lingling Yang, Jen Q. Pan & Slobodan M. Todorovic. Global genetic deletion of CaV3.3 channels facilitates anaesthetic induction and enhances isoflurane-sparing effects of T-type calcium channel blockers. Scientific Reports 2020, 10: 21510
Chemin J, Timic Stamenic T, Cazade M, Llinares J, Blesneac I, Todorovic SM, Lory P. A novel phospho-modulatory mechanism contributes to the calcium-dependent regulation of T-type Ca2+ channels. Scientific Reports 9
Woodward TJ, Timic Stamenic T, Todorovic SM. Neonatal general anesthesia causes lasting alterations in excitatory and inhibitory synaptic transmission in the ventrobasal thalamus of adolescent female rats. Neurobiol Dis. 2019 Jul;127:472-481. PubMed PMID: 30825640
Timic Stamenic T, Feseha S, Valdez R, Zhao W, Klawitter J, Todorovic SM. Alterations in Oscillatory Behavior of Central Medial Thalamic Neurons Demonstrate a Key Role of CaV3.1 Isoform of T-Channels During Isoflurane-Induced Anesthesia. Cereb Cortex. 2019 Dec 17;29(11):4679-4696. PubMed PMID: 30715245
Tracy ME, Tesic V, Stamenic TT, Joksimovic SM, Busquet N, Jevtovic-Todorovic V, Todorovic SM. Ca(V)3.1 isoform of T-type calcium channels supports excitability of rat and mouse ventral tegmental area neurons. Neuropharmacology. 2018 Jun;135:343-354. PubMed PMID: 29578032
Stamenic TT, Poe MM, Rehman S, Santrac A, Divovic B, Scholze P, Ernst M, Cook JM, Savic MM. Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABA(A) receptors containing the a5 subunit. Eur J Pharmacol. 2016 Nov 15;791:433-443. PubMed PMID: 27639297
Batinic B, Santrac A, Divovic B, Timic T, Stankovic T, Obradovic ALj, Joksimovic S, Savic MM. Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring. Behav Brain Res. 2016 Feb 15;299:72-80. PubMed PMID: 26620494
Ðordevic SM, Cekic ND, Savic MM, Isailovic TM, Randelovic DV, Markovic BD, Savic SR, Timic Stamenic T, Daniels R, Savic SD. Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. Int J Pharm. 2015 Sep 30;493(1-2):40-54. PubMed PMID: 26209070
Timic Stamenic T, Joksimovic S, Biawat P, Stankovic T, Markovic B, Cook JM, Savic MM. Negative modulation of a5 GABAA receptors in rats may partially prevent memory impairment induced by MK-801, but not amphetamine- or MK-801-elicited hyperlocomotion. J Psychopharmacol. 2015 Sep;29(9):1013-24. PubMed PMID: 26105958
Kovacevic J, Timic T, Tiruveedhula VV, Batinic B, Namjoshi OA, Milic M, Joksimovic S, Cook JM, Savic MM. Duration of treatment and activation of a1-containing GABAA receptors variably affect the level of anxiety and seizure susceptibility after diazepam withdrawal in rats. Brain Res Bull. 2014 May;104:1-6. PubMed PMID: 24695241
Joksimovic S, Varagic Z, Kovacevic J, Van Linn M, Milic M, Rallapalli S, Timic T, Sieghart W, Cook JM, Savic MM. Insights into functional pharmacology of a1 GABA(A) receptors: how much does partial activation at the benzodiazepine site matter?. Psychopharmacology (Berl). 2013 Nov;230(1):113-23. PubMed PMID: 23685860
Joksimovic S, Divljakovic J, Van Linn ML, Varagic Z, Brajkovic G, Milinkovic MM, Yin W, Timic T, Sieghart W, Cook JM, Savic MM. Benzodiazepine-induced spatial learning deficits in rats are regulated by the degree of modulation of a1 GABA(A) receptors. Eur Neuropsychopharmacol. 2013 May;23(5):390-9. PubMed PMID: 22633616
Milic M, Timic T, Joksimovic S, Biawat P, Rallapalli S, Divljakovic J, Radulovic T, Cook JM, Savic MM. PWZ-029, an inverse agonist selective for a5 GABAA receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. Behav Brain Res. 2013 Mar 15;241:206-13. PubMed PMID: 23261875
Timic T, Joksimovic S, Milic M, Divljakovic J, Batinic B, Savic MM. Midazolam impairs acquisition and retrieval, but not consolidation of reference memory in the Morris water maze. Behav Brain Res. 2013 Mar 15;241:198-205. PubMed PMID: 23261388
Divljakovic J, Milic M, Namjoshi OA, Tiruveedhula VV, Timic T, Cook JM, Savic MM. ßCCT, an antagonist selective for a(1)GABA(A) receptors, reverses diazepam withdrawal-induced anxiety in rats. Brain Res Bull. 2013 Feb;91:1-7. PubMed PMID: 23149168
Milic M, Divljakovic J, Rallapalli S, van Linn ML, Timic T, Cook JM, Savic MM. The role of a1 and a5 subunit-containing GABAA receptors in motor impairment induced by benzodiazepines in rats. Behav Pharmacol. 2012 Apr;23(2):191-7. PubMed PMID: 22327019
Divljakovic J, Milic M, Timic T, Savic MM. Tolerance liability of diazepam is dependent on the dose used for protracted treatment. Pharmacol Rep. 2012;64(5):1116-25. PubMed PMID: 23238468