Sample of Active Projects in the Lab
Xylazine
Xylazine is in the unregulated drug supply at increasing rates, usually combined with fentanyl, necessitating understanding of its pharmacology. Despite commentary from politicians, and public health officials, it is unknown how xylazine impacts naloxone efficacy, and. few studies have examined it alone. Here, we examine the impact of xylazine alone and in combination with fentanyl on several behaviors in mice. Surprisingly, naloxone precipitates withdrawal from xylazine and fentanyl/xylazine coadministration, with enhanced sensitivity in females. Further, xylazine is a full agonist at kappa opioid receptors, a potential mechanism for its naloxone sensitivity. Finally, we demonstrate surprising effects of xylazine to kappa opioid antagonism, which are relevant for public health considerations. These data address an ongoing health crisis and will help inform critical policy and healthcare decisions.
Most recent publication:
Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism Madigan L Bedard, Xi-Ping Huang, Jackson G Murray, Alexandra C Nowlan, Sara Y Conley, Sarah E Mott, Samuel J Loyack, Calista A Cline, Caroline G Clodfelter, Nabarun Dasgupta, Brian Krumm, Bryan L Roth, Zoe A McElligott
PMID: 39086495
PMCID: PMC11290297
DOI: 10.1016/j.addicn.2024.100155
Norepinephrine
Norepinephrine (NE) is a catecholamine produced by multiple cell clusters in the pons and medula (as well as sympathetic ganglia and adrenal gland). We are interested in how NE modulates learning and memory, stress responsivity, anxiety, drug and alcohol use, and other behaviors. In particular we're interested in how NE modulates the bed nucleus of the stria terminalis, a component of the extended amygdala receiving the densest NE innervation in the brain!
Most recent publication:
Stress-induced alterations of norepinephrine release in the bed nucleus of the stria terminalis of mice Karl T Schmidt, Viren H Makhijani, Kristen M Boyt, Elizabeth S. Cogan, Dipanwita Pati, Melanie M Pina, Isabel M Bravo, Jason L Locke, Sara R Jones, Joyce Besheer, Zoe A McElligott ACS Chemical Neuroscience (2019) April 17; 10(4): 1872-1874
bioRxiv link
ACS chemical Neuroscience link
Opioids
Opioid use disorder (OUD) is a chronically relapsing condition where persons take opioids (either prescription or illicit) to circumvent the negative reinforcing properties associated with opioid withdrawal. Withdrawal from opioids has an acute phase as well as lasting symptoms well into protracted abstinence. Our lab is interested in the plasticity that underlies opioid withdrawal behaviors at both the acute and protracted time points. Specifically we are interested in weight loss, sleep dysregulation, and anxiety-like behaviors.
Most recent publication:
Divergent Behavioral Responses in Protracted Opioid Withdrawal in Male and Female C57BL/6J Mice
Bravo IM, Luster BR, Flanigan ME, et al. Divergent behavioral responses in protracted opioid withdrawal in male and female C57BL/6J mice. Eur J Neurosci. 2020;51(3):742-754. doi:10.1111/ejn.14580
Funding
Selected Peer-reviewed Publications
All publications from Zoe: https://www.ncbi.nlm.nih.gov/myncbi/zoe.mcelligott.1/bibliography/public/ https://scholar.google.com/citations?hl=en&user=sUeBSIoAAAAJ
Yu W, Pati D, Pina MM, Schmidt KT, Boyt KM, Hunker AC, Zweifel LS, McElligott ZA, Kash TL. Periaqueductal gray/dorsal raphe dopamine neurons contribute to sex differences in pain-related behaviors. Neuron (2021) Apr 21
Torruella-Suárez ML, Vandenberg JR, Cogan ES, Tipton GJ, Teklezghi A, Dange K, Patel GK, McHenry JA, Hardaway JA, Kantak PA, Crowley NA, DiBerto JF, Faccidomo SP, Hodge CW, Stuber GD, McElligott ZA. Manipulations of Central Amygdala Neurotensin Neurons Alter the Consumption of Ethanol and Sweet Fluids in Mice. J Neurosci (2020) Jan 15
Hardaway JA, Halladay LR, Mazzone CM, Pati D, Bloodgood DW, Kim M, Jensen J, DiBerto JF, Boyt KM, Shiddapur A, Erfani A, Hon OJ, Neira S, Stanhope CM, Sugam JA, Saddoris MP, Tipton G, McElligott Z, Jhou TC, Stuber GD, Bruchas MR, Bulik CM, Holmes A, Kash TL. Central Amygdala Prepronociceptin-Expressing Neurons Mediate Palatable Food Consumption and Reward. Neuron (2019) Jun 5
Mazzone, CM, Pati, D, Michaelides, M, DiBerto, J, Fox, JH, Tipton, G, Anderson, C, Duffy, K, McKlveen, JM, Hardaway, JA, Magness, S. T, Falls, W. A, Hammack, S. E, McElligott, ZA, Hurd, YL, & Kash, TL. Acute engagement of Gq-mediated signaling in the bed nucleus of the stria terminalis induces anxiety-like behavior (2018)
Radke AK, Jury NJ, Kocharian A, Marcinkiewcz CA, Lowery-Gionta EG, Pleil KE, McElligott ZA, McKlveen JM, Kash TL, Holmes A. Chronic EtOH effects on putative measures of compulsive behavior in mice (2017) Mar 22
McHenry JA, Otis JM, Rossi MA, Robinson JE, Kosyk O, Miller NW, McElligott ZA, Budygin EA, Rubinow DR, Stuber GD. Hormonal gain control of a medial preoptic area social reward circuit (2017) Mar 20
McCall JG, Siuda ER, Bhatti DL, Lawson LA, McElligott ZA, Stuber GD, Bruchas MR. Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior (2017) Jul 14
Sciolino NR, Plummer NW, Chen YW, Alexander GM, Robertson SD, Dudek SM, McElligott ZA, Jensen P. Recombinase-Dependent Mouse Lines for Chemogenetic Activation of Genetically Defined Cell Types. Cell Rep (2016) Jun 14
Marcinkiewcz CA, Mazzone CM, D'Agostino G, Halladay LR, Hardaway JA, DiBerto JF, Navarro M, Burnham N, Cristiano C, Dorrier CE, Tipton GJ, Ramakrishnan C, Kozicz T, Deisseroth K, Thiele TE, McElligott ZA, Holmes A, Heisler LK, Kash TL. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature (2016) Sep 1
Berrios J, Stamatakis AM, Kantak PA, McElligott ZA, Judson MC, Aita M, Rougie M, Stuber GD, Philpot BD Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimualtion (2016) Feb 12
Li C, Sugam JA, Lowery-Gionta EG, McElligott ZA, McCall NM, Lopez AJ, McKlveen JM, Pleil KE, Kash TL Mu Opioid Receptor Modulation of Dopamine Neurons in the Periaqueductal Gray/Dorsal Raphe: A Role in Regulation of Pain (2016) Jan 21
Kash TL, Pleil KE, Marcinkiewcz CA, Lowery-Gionta EG, Crowley N, Mazzone C, Sugam J, Hardaway JA, McElligott ZA. Neuropeptide regulation of signaling and behavior in the BNST. Mol Cells (2015) Jan 31
Radke AK, Jury NJ, Marcinkiewcz CA, Lowery-Gionta EG, Pleil KE, McElligott ZA, McKlveen JM, Kash TL, Holmes A Chronic EtOH effects on putative measures of compulsive behavior in mice (2015) Dec 12
McElligott Z Optogenetic and Chemogenetic Approaches to Advance Monitoring Molecules ACS Chemical Neuroscience (2015) Jul 15;6(7):944-7
Stamatakis AM, Sparta DR, Jennings JH, McElligott ZA, Decot H, Stuber GD. Amygdala and bed nucleus of the stria terminalis circuitry: Implications for addiction-related behaviors. Neuropharmacology (2014)
McElligott ZA, Fox ME, Walsh PL, Urban DJ, Ferrel MS, Roth BL, Wightman RM Noradrenergic Synaptic Function in the Bed Nucleus of the Stria Terminalis Varies in Animal Models of Anxiety and Addiction. Neuropsychopharmacology (2013) Aug: 38 (9): 1665-73.
Walsh PL, Kile BM, McElligott ZA, Bucher ES, Salahpour A, Caron MG, Wightman RM Improving the Temporal Resolution of Fast-Scan Cyclic Voltammetry. ACS Chemical Neuroscience (2012) April; 3(4):285-292
Herr NR, Park JW, McElligott ZA, Belle AM, Carelli RM and Wightman RM In Vivo Voltammetry Monitoring of Electrically Evoked Extracellular Norepinephrine in Subregions of the Bed Nucleus of the Stria Terminalis.Journal of Neurophysiology (2012) March; 107(6):1731-7
McElligott ZA, Klug J, Nobis W, Patel S, Grueter BA, Kash TL and Winder DG. Distinct forms of Gq-receptor-dependent plasticity of excitatory transmission in the BNST are differentially affected by stress.Proceedings of the National Academy of Sciences (2010) Feb 2; 107 (5)
McElligott ZA, Winder DG. Modulation of glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Prog Neuropsychopharmacol Biol Psychiatry (2009) Nov 13
McElligott ZA and Winder DG, α1-adrenergic receptors induce heterosynaptic long term depression of excitatory transmission in the bed nucleus of the stria terminalis that is disrupted in mouse models of affective disorder. Neuropsychopharmacology (2008) Sep: 33(10):2313-23.