CONTACT INFORMATION http://www.loyola.org
George Battaglia
Ph.D.
  • Professor
  • Molecular Pharmacology and Therapeutics
Research Summary

Effects of drugs of abuse and anti-depressants on serotonin function during development

Serotonin (5-HT) systems play a prominent role in a number of physiologic functions and clinical disorders. Dysfunction in 5-HT systems has been implicated in mood disorders such as anxiety and depression. In addition, profound changes in 5-HT function can be produced by drugs of abuse, such as methamphetamine, MDMA and cocaine. Our research program has focused on the study of brain serotonergic systems with respect to issues concerning 5-HT receptor-mediated signal transduction and drug-induced neuroadaptive changes at different developmental ages. More specifically, we have been interested in the following: (1) investigating 5-HT1A receptor signaling of hormone and kinase pathways in hypothalamic neuroendocrine neurons (2) delineating the mechanism of regulation of serotonin receptor subtypes and receptor-mediated signal transduction in response to therapeutic agents and drugs of abuse; (3) determining the consequences of prenatal exposure to antidepressants or cocaine on serotonergic function in young and adult offspring; (4) elucidating the consequences of early developmental exposure to drugs of abuse and clinically prescribed drugs on the immediate and long-term functional status of 5-HT systems;(5) delineating the mechanisms of 5-HT receptor “cross-talk” and heterologous desensitization between 5-HT1A and 5-HT2A receptors on neuroendocrine neurons, (6) investigating the intracellular mechanisms mediating the desensitization in forebrain 5-HT1A receptor signaling produced by serotonin selective reuptake inhibitors (SSRIs) such as fluoxetine and other serotonin altering drugs; and (7) understanding the effects of acute and chronic cocaine on 5-HT systems and the mechanisms mediating withdrawal-induced supersensitivity in 5-HT2A receptor systems. Given the increasing use of clinically prescribed drugs across all age groups, these studies may have significant implications with respect to understanding the long-term consequences in serotonin signaling and function due to drug exposure at different developmental ages.

Publications

Extra-nuclear estrogen receptor GPR30 regulates serotonin function in rat hypothalamus.Xu,H.; Qin,S.; Carrasco,G. A.; Dai,Y.; Filardo,E. J.; Prossnitz,E. R.; Battaglia,G.; Doncarlos,L. L.; Muma,N. A.Neuroscience 2009 ;158(4):1599-1607

Prolonged 5-HT1A/5-HT2A receptor cross-talk is absent prior to adulthood in rats.Petrunich,M. L.; Garcia,F.; Carrasco,G. A.; Battaglia,G.Neuroreport 2008 ;19(15):1457-1461

Sustained treatment with a 5-HT(2A) receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT(2A) receptors despite increases in receptor protein levels in ratsShi,J.; Landry,M.; Carrasco,G. A.; Battaglia,G.; Muma,N. A.Neuropharmacology 2008 ;55(5):687-692

Withdrawal from a single exposure to cocaine increases 5-HT2A receptor and G protein function.Carrasco,G. A.; Battaglia,G.Neuroreport 2007 ;18(1):51-55

Single exposure to a serotonin 1A receptor agonist, (+)8-hydroxy-2-(di-n-propylamino)-tetralin, produces a prolonged heterologous desensitization of serotonin 2A receptors in neuroendocrine neurons in vivo.Carrasco,G. A.; Van de Kar,L. D.; Jia,C.; Xu,H.; Chen,Z.; Chadda,R.; Garcia,F.; Muma,N. A.; Battaglia,G.Journal of Pharmacology & Experimental Therapeutics 2007 ;320(3):1078-1086

Agonist induced-phosphorylation of Galpha11 protein reduces coupling to 5-HT2A receptors.Shi,J.; Damjanoska,K. J.; Singh,R. K.; Carrasco,G. A.; Garcia,F.; Grippo,A. J.; Landry,M.; Sullivan,N. R.; Battaglia,G.; Muma,N. A.Journal of Pharmacology & Experimental Therapeutics 2007 ;323(1):248-256

Chronic olanzapine activates the Stat3 signal transduction pathway and alters expression of components of the 5-HT2A receptor signaling system in rat frontal cortex.Muma,N. A.; Singh,R. K.; Vercillo,M. S.; D'Souza,D. N.; Zemaitaitis,B.; Garcia,F.; Damjanoska,K. J.; Zhang,Y.; Battaglia,G.; Van de Kar,L. D.Neuropharmacology 2007 ;53(4):552-562

5-HT1A receptors mediate (+)8-OH-DPAT-stimulation of extracellular signal-regulated kinase (MAP kinase) in vivo in rat hypothalamus: time dependence and regional differences.Crane,J. W.; Shimizu,K.; Carrasco,G. A.; Garcia,F.; Jia,C.; Sullivan,N. R.; D'Souza,D. N.; Zhang,Y.; Van de Kar,L. D.; Muma,N. A.; Battaglia,G.Brain research 2007 ;1183( ):51-59

Alterations in 5-HT2A receptor signaling in male and female transgenic rats over-expressing either Gq or RGS-insensitive Gq protein.Shi,J.; Damjanoska,K. J.; Zemaitaitis,B.; Garcia,F.; Carrasco,G.; Sullivan,N. R.; She,Y.; Young,K. H.; Battaglia,G.; Van De kar,L. D.; Howland,D. S.; Muma,N. A.Neuropharmacology 2006 ;51(3):524-535

Cocaine-mediated supersensitivity of 5-HT2A receptors in hypothalamic paraventricular nucleus is a withdrawal-induced phenomenon.Carrasco,G. A.; Van de Kar,L. D.; Sullivan,N. R.; Landry,M.; Garcia,F.; Muma,N. A.; Battaglia,G.Neuroscience 2006 ;143(1):7-13

Fluoxetine treatment of prepubescent rats produces a selective functional reduction in the 5-HT2A receptor-mediated stimulation of oxytocin.Landry,M.; Frasier,M.; Chen,Z.; Van De Kar,L. D.; Zhang,Y.; Garcia,F.; Battaglia,G.Synapse 2005 ;58(2):102-109

Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine.Chen,Z.; Tetzlaff,J.; Sripathirathan,K.; Carrasco,G. A.; Shankaran,M.; Van De Kar,L. D.; Muma,N. A.; Battaglia,G.Psychopharmacology 2005 ;180(2):316-326

Prenatal cocaine exposure potentiates paroxetine-induced desensitization of 5-HT2A receptor function in adult male rat offspring.Chen,Z.; Waimey,K.; Van de Kar,L. D.; Carrasco,G. A.; Landry,M.; Battaglia,G.Neuropharmacology 2004 ;46(7):942-953

Agonist-induced serotonin 2A receptor desensitization in the rat frontal cortex and hypothalamus.Damjanoska,K. J.; Heidenreich,B. A.; Kindel,G. H.; D'Souza,D. N.; Zhang,Y.; Garcia,F.; Battaglia,G.; Wolf,W. A.; Van de Kar,L. D.; Muma,N. A.Journal of Pharmacology & Experimental Therapeutics 2004 ;309(3):1043-1050

Estrogen reduces serotonin-1A receptor-mediated oxytocin release and Galpha(i/o/z) proteins in the hypothalamus of ovariectomized rats.D'Souza,D. N.; Zhang,Y.; Damjanoska,K. J.; Carrasco,G. A.; Sullivan,N. R.; Garcia,F.; Battaglia,G.; Doncarlos,L. L.; Muma,N. A.; Van de Kar,L. D.Neuroendocrinology 2004 ;80(1):31-41

Fluoxetine-induced changes in body weight and 5-HT1A receptor-mediated hormone secretion in rats on a tryptophan-deficient diet.D'Souza,D. N.; Zhang,Y.; Garcia,F.; Battaglia,G.; Van de Kar,L. D.American Journal of Physiology - Regulatory Integrative & Comparative Physiology 2004 ;286(2):R390-7

Desensitization of 5-HT1A receptors by 5-HT2A receptors in neuroendocrine neurons in vivo.Zhang,Y.; Gray,T. S.; D'Souza,D. N.; Carrasco,G. A.; Damjanoska,K. J.; Dudas,B.; Garcia,F.; Zainelli,G. M.; Sullivan Hanley,N. R.; Battaglia,G.; Muma,N. A.; Van de Kar,L. D.Journal of Pharmacology & Experimental Therapeutics 2004 ;310(1):59-66

Limbic pallidal adaptations following long-term cessation of dopaminergic transmission: lack of upregulation of dopamine receptor function.Heidenreich,B. A.; Mitrovic,I.; Battaglia,G.; Napier,T. C.Experimental neurology 2004 ;186(2):145-157

Short-term cocaine treatment causes neuroadaptive changes in Galphaq and Galpha11 proteins in rats undergoing withdrawal.Carrasco,G. A.; Damjanoska,K. J.; D'Souza,D. N.; Zhang,Y.; Garcia,F.; Battaglia,G.; Muma,N. A.; Van de Kar,L. D.Journal of Pharmacology & Experimental Therapeutics 2004 ;311(1):349-355

A region-specific increase in Galphaq and Galpha11 proteins in brains of rats during cocaine withdrawal.Carrasco,G. A.; Zhang,Y.; Damjanoska,K. J.; D'Souza,D. N.; Garcia,F.; Battaglia,G.; Muma,N. A.; Van de Kar,L. D.Journal of Pharmacology & Experimental Therapeutics 2003 ;307(3):1012-1019

Chronic fluoxetine differentially affects 5-hydroxytryptamine (2A) receptor signaling in frontal cortex, oxytocin- and corticotropin-releasing factor-containing neurons in rat paraventricular nucleus.Damjanoska,K. J.; Van de Kar,L. D.; Kindel,G. H.; Zhang,Y.; D'Souza,D. N.; Garcia,F.; Battaglia,G.; Muma,N. A.Journal of Pharmacology & Experimental Therapeutics 2003 ;306(2):563-571

Treatment of cycling female rats with fluoxetine induces desensitization of hypothalamic 5-HT(1A) receptors with no change in 5-HT(2A) receptorsVan de Kar,L. D.; Raap,D. K.; Battaglia,G.; Muma,N. A.; Garcia,F.; DonCarlos,L. L.Neuropharmacology 2002 ;43(1):45-54

Ovariectomy-induced increases in hypothalamic serotonin-1A receptor function in rats are prevented by estradiolRaap,D. K.; DonCarlos,L. L.; Garcia,F.; Zhang,Y.; Muma,N. A.; Battaglia,G.; Van de Kar,L. D.Neuroendocrinology 2002 ;76(6):348-356

Evidence that 5-HT2A receptors in the hypothalamic paraventricular nucleus mediate neuroendocrine responses to (-)DOIZhang,Y.; Damjanoska,K. J.; Carrasco,G. A.; Dudas,B.; D'Souza,D. N.; Tetzlaff,J.; Garcia,F.; Hanley,N. R.; Scripathirathan,K.; Petersen,B. R.; Gray,T. S.; Battaglia,G.; Muma,N. A.; Van de Kar,L. D.The Journal of neuroscience : the official journal of the Society for Neuroscience 2002 ;22(21):9635-9642

Destruction of serotonergic nerve terminals prevents fluoxetine-induced desensitization of hypothalamic 5-HT(1A) receptorsD'Souza,D. N.; Zhang,Y.; Garcia,F.; Battaglia,G.; Van De Kar,L. D.Psychopharmacology 2002 ;164(4):392-400

Characterization of the functional heterologous desensitization of hypothalamic 5-HT(1A) receptors after 5-HT(2A) receptor activationZhang,Y.; D'Souza,D.; Raap,D. K.; Garcia,F.; Battaglia,G.; Muma,N. A.; Van de Kar,L. D.The Journal of neuroscience : the official journal of the Society for Neuroscience 2001 ;21(20):7919-7927

Neurochemical changes in brain serotonin neurons in immature and adult offspring prenatally exposed to cocaineCabrera-Vera,T. M.; Garcia,F.; Pinto,W.; Battaglia,G.Brain research 2000 ;870(1-2):1-9

5-HT(1A) and 5-HT(2A) serotonin receptor turnover in adult rat offspring prenatally exposed to cocaineVicentic,A.; Cabrera-Vera,T. M.; Pinto,W.; Battaglia,G.Brain research 2000 ;877(2):141-148

Estrogen desensitizes 5-HT(1A) receptors and reduces levels of G(z), G(i1) and G(i3) proteins in the hypothalamusRaap,D. K.; DonCarlos,L.; Garcia,F.; Muma,N. A.; Wolf,W. A.; Battaglia,G.; Van de Kar,L. D.Neuropharmacology 2000 ;39(10):1823-1832

Evidence that G(z)-proteins couple to hypothalamic 5-HT(1A) receptors in vivoSerres,F.; Li,Q.; Garcia,F.; Raap,D. K.; Battaglia,G.; Muma,N. A.; Van de Kar,L. D.The Journal of neuroscience : the official journal of the Society for Neuroscience 2000 ;20(9):3095-3103

Coadministration of 5-hydroxytryptamine(1A) antagonist WAY-100635 prevents fluoxetine-induced desensitization of postsynaptic 5-hydroxytryptamine(1A) receptors in hypothalamusSerres,F.; Muma,N. A.; Raap,D. K.; Garcia,F.; Battaglia,G.; Van de Kar,L. D.The Journal of pharmacology and experimental therapeutics 2000 ;294(1):296-301

Long-term fluoxetine produces behavioral anxiolytic effects without inhibiting neuroendocrine responses to conditioned stress in ratsZhang,Y.; Raap,D. K.; Garcia,F.; Serres,F.; Ma,Q.; Battaglia,G.; Van de Kar,L. D.Brain research 2000 ;855(1):58-66

Prenatal cocaine exposure potentiates 5-HT(2a) receptor function in male and female rat offspringBattaglia,G.; Cabrera-Vera,T. M.; Van De Kar,L. D.Synapse (New York, N.Y.) 2000 ;35(3):163-172