Dr. Mohamed  Kabbaj

3300H MSR
Florida State University
College of Medicine
1115 West Call Street
Tallahassee, FL 32306-4300
(850) 644-4930

Ph.D.
University of Bordeaux II, France
1997

 
Postdoctoral Associates
  Dr. Florian  Duclot Dr. Florian Duclot
3300 MSR
(850) 645-2925

  Dr. Ambalika  Sarkar Dr. Ambalika Sarkar
3300 MSR
(850) 644-3076

 
Graduate Students
  Amanda  Dossat Amanda Dossat
3310 MSR
(850) 645-8719

  Lindsay  Elvir Lindsay Elvir
3300 MSR
(850) 645-2920

  Samantha  Saland Samantha Saland
3310 MSR
(850) 644-4930

  Kristin  Schoepfer Kristin Schoepfer
3300 MSR
(850) 644-3076

  Caroline  Strong Caroline Strong

(850) 644-3076

  Katherine  Wright Katherine Wright
3310 MSR
(850) 645-2920

 
Lab Technicians
  Hui  Wang Hui Wang

(850) 644-3076

Dr. Mohamed Kabbaj

Professor of Biomedical Science & Neuroscience

Dr. Mohamed Kabbaj is currently accepting new graduate students for Fall 2016

Research Interest

The focus of our research is to understand the neurobiology underlying individual differences and sex differences in depression and drug addiction. Another focus of our research is to examine epigenetic mechanisms underlying social behaviors. Below are some examples of ongoing/past studies:

When compared to LR rats, HR rats pretreated with amphetamine express more dopamine transporter mRNA.

Neurobiological basis of individual differences in behavioral sensitization to amphetamine

The overall aim of this work is to investigate the neurobiological basis of behavioral sensitization to amphetamine in the context of individual differences. We aim to understand the interplay between psychosocial stress and the development of behavioral sensitization to amphetamine in the context of individual differences using a model of novelty seeking behavior that distinguishes outbred rats on the basis of their high (High Responder, HR) or low (Low Responder, LR) locomotor activity in a novel environment. HR rats acquire AMPH and cocaine self-administration faster than LR rats (Kabbaj et al., 2001; Mantsch et al., 2001; Marinelli and White, 2000; Piazza et al., 1989; Piazza et al., 2000; Pierre and Vezina, 1997) and show a greater behavioral sensitization to amphetamine or cocaine after repeated administration of low doses (Hooks et al., 1992; Hooks et al., 1991a; Piazza et al., 1989; Pierre and Vezina, 1997). Behavioral and neural sensitization may have a potential role in the pathogenesis of affective disorders and drug abuse (Robinson and Berridge, 2000; White and Kalivas, 1998).

One possible mechanism by which stress enhances drug taking and behavioral sensitization to psychostimulants is through an interaction between glucocorticoids and dopamine. Our working hypothesis is that differences in stress- and dopamine- related genes play a role in HR and LR behavioral differences in sensitization to AMPH, as well as in the effect of psychosocial stress on behavioral sensitization to AMPH. To test these hypotheses, we will describe the neurobiological basis of behavioral sensitization to amphetamine as well as the neurobiological basis of the effect of psychosocial stress (and glucocorticoids) on behavioral sensitization to AMPH in the context of individual differences.

Epigenetics of social defeat

Epigenetics of social defeat:

Histone acetylation and methylation, as well as deacetylation and demythylation are epigenetic states that can produce activation or silencing of specific genes. These post-translational processes have been shown to occur in the brain and to affect gene expression. Our preliminary studies show that there exist basal differences in the overall degree of acetylation of H3K14 and H2b, but not H4, in rats that differ in response to novelty. Indeed, the high responders rats (HR) exhibit higher levels of acetylation of H3K14 and H2b when compared to low responders rats (LR). Interestingly, chronic social defeat, which is an established animal model of depression, induces a differential acetylation of H3K14 and H2b in HR and LR rats. Social defeat decreases the acetylation levels on H3K14 and H2b in HR rats and increases it in the LR rats. Social defeat however decreased the level of acetylation of H4 independently of HR and LR rats. Since HR and LR rats exhibit different emotional responses, with the HR rats more prone to depression-like phenomena, we hypothesize that the epigenetic states described for the H3K14 and H2b contribute to individual differences in response to novelty and to individual differences in response to chronic stress-induced psychopathology.

Epigenetics of social bonding

Epigenetics of social bonding:

Social attachments are a vital part of healthy human behavior and an inability to form such attachments is regarded as a symptom of mental disorders such as schizophrenia and autism. Studying the mechanisms underlying social attachment requires an animal model that displays behaviors similar to that of human social attachment. Prairie voles (Microtus ochrogaster) have become an important model for the study of the neurobiology of social attachment. In the field, male and female prairie voles form long-term bonds and share a nest throughout the breeding season. Such a breeding pair typically remains together until one animal dies. For prairie voles, it has been demonstrated that 24 h of mating reliably results in partner preference formation, whereas 6 h of cohabitation in the absence of mating does not induce this behavior. Given that mating in prairie voles induces neuroadaptations that eventually lead to bonding, we are investigating whether mating induced social bonding has an underlying epigenetic basis

Sex differences in anxiety: role of EGR I

Sex differences in anxiety: role of EGR I

In this proposal we are investigating sex differences in social interaction (SI) behavior and we are examining the role of the immediate early gene zif268 in the medial prefrontal cortex (mPFC) in mediating these behaviors in male and female rats. Another focus of this study is to determine the upstream and downstream molecular targets of zif268 that are relevant to sex differences in SI. In our hands, male rats exhibit higher SI than female rats -regardless of their estrus cycle-. Interestingly, the basal expression of zif268 in the medial prefrontal cortex (mPFC) varied between the sexes in that males had higher levels of zif268 expression in this region when compared to females. Through the use of zif268 antisense oligodeoxynucleotides (zif268 ASO), we induced a temporary down-regulation of zif268 expression in the mPFC of male rats and compared their SI behavior to both control males and females infused with zif268 missense oligodeoxynucleotides (zif268 MSO). Upon doing this, we found that zif268 ASO males displayed significantly less SI (and therefore, were more anxious) than control males and, in fact, displayed levels of SI which were similar to control females. In essence, down-regulation of zif268 expression in the mPFC of male rats eliminated the sex differences previously found in anxiety-like behavior in the SI test. Our novel findings have led us to hypothesize that sexually-dimorphic zif268 expression in the mPFC is a key molecular factor in mediating sex-specific in anxiety-like behavior in the SI test, which has a strong social component. We are exploring further the hypothesis that zif268 in the medial prefrontal cortex play a major role in determining sex differences in SI and determine the upstream and downstream targets of zif268 in the mPFC that play a major role in these sex differences in anxiety.

Testosterone and Depression

Testosterone and Depression

Testosterone has mood-enhancing properties and antidepressant effects in men. In fact, increased incidence of hypogonadism occurs in men with major depressive disorder (MDD), and testosterone replacement effectively improves mood. In rodents, testosterone has antidepressant effects in aged male mice and protective effects against the development of depression-like behaviors in rats. Our studies suggest a modulatory role for testosterone in the regulation of depressive disorders; and proposed molecular mechanisms and brain sites of its actions. For example, we have recently shown that testosterone antidepressant effects are lost if we enhance gene expression of a dominant negative form of ERK2 (an important molecule in the MAPK pathway) in the hippocampus (see attached figure).

Techniques used in Dr. Kabbaj’s Laboratory

Molecular

  • In situ hybridization (single and double)
  • Immunohistochemistry
  • Radioimmunoassays
  • Westerm Blot
  • Microarray
  • RT-PCR and quantitative real time RT-PCR
  • ChIP assays
  • ChIP on chips
  • Chip-sequencing

Behavioral

  • Locomotor activity/Sensitization
  • Tests of anxiety (Light dark box, elevated plus maze, open field, Social Interaction)
  • Tests for learning and memory
  • Conditioned place preference
  • Operant chambers of drug self-administration

Actual Funding

1 R01 MH087583-01A1 (Kabbaj) 9/1/2010-8/30/2015
NIMH/NIH
Sex differences in anxiety: role of zif268
The major aim of this application is to examine the role of zif268 in the prefrontal cortex in determining sex differences in anxiety in rats.

1 RO1 MH099085-01A1 (Kabbaj) 7/1/2013- 6/30-2018
Sex differences in ketamine antidepressant effects
The major aim of this work is to determine the neurobiology behind sex differences in ketamine antidepressant effects.

Selected Recent Publications

Wright KN, Hollis F, Duclot F, Dossat AM, Strong CE, Francis TC, Mercer R, Feng J, Dietz DM, Lobo MK, Nestler EJ, Kabbaj M. Methyl supplementation attenuates cocaine-seeking behaviors and cocaine-induced c-fos activation in a DNA methylation-dependent manner.. J Neurosci. 10; 35(23):8948-58. (2015)
McHenry JA, Carrier N, Hull EM, Kabbaj M. Sex differences in anxiety and depression: Role of testosterone.. Frontiers in Neuroendocrinology. 35:42-56. (2014)
Hollis F and Kabbaj M. Social defeat as an animal model for depression.. ILAR J. 55 (2): 221-232. (2014)
Carrier N and Kabbaj M. Sex differences in the antidepressant effects of ketamine.. Neuropharmacology. 70: 27-34. (2013)
Jourdi H and Kabbaj M. Acute BDNF treatment upregulates GluR1-SAP97 and GluR2-GRIP1 interactions: implications for sustained AMPA receptor expression.. PLoS ONE. 8 (2): e57124. (2013)
Duclot F and Kabbaj M. Individual differences in novelty seeking predict subsequent vulnerability to social defeat through a differential epigenetic regulation of brain-derived neurotrophic factor expression.. Journal of Neuroscience. 33(27): 11048-11060. (2013)
Hollis F, Gaval M, Carrier N, Dietz D and Kabbaj M . Juvenile And Adult Rats Differ In Cocaine Reward And Expression Of Zif268 In The Forebrain. Neuroscience. 200: 91-8. (2012)
Carrier N and Kabbaj M . Testosterone and imipramine have antidepressant effects in socially isolated male but not female rats.. Hormones and Behavior. in press. (2012)
Carrier N and Kabbaj M . Extracellular signal-regulated kinase 2 signaling in the hippocampus dentate gyrus mediates the antidepressant effects of testosterone.. Biological Psychiatry. 71(1) 642-51. (2012)
Duclot F, Hollis F, Darcy MJ and Kabbaj M. Individual differences in novelty-seeking behavior in rats as a model for psychosocial stress-related mood disorders. Physiology and Behavior. 104 (2): 296-305. (2011)
Hollis F, Duclot F, Gunjan A and Kabbaj M. Individual differences in the effect of social defeat on anhedonia and histone acetylation in the rat hippocampus. Hormones and Behaviors. (3):331-337. (2011)
Young KA, Liu Y, Gobrogge KL, Wang H, Kabbaj M and Wang Z. Amphetamine alters behavior and mesocorticolimbic dopamine receptor expression in the monogamous female prairie vole. Brain Research. 1376:213-222. (2011)
Calvo N*, Cecchi M*, Kabbaj M*, Watson SJ, Akil H. Differential effects of social defeat in rats with high and low locomotor response to novelty. Neuroscience. (2011) [in press | *=co-first authors]
Radley JJ, Kabbaj M, Jacobson L, Heydendael W and Herman JP. Stress risk factors and stress-related pathology: neuroplasticity, epigenetics and endophenotypes.. Stress. 14 (5): 481-497. (2011) [All authors contributed equally]
Liu Y, Aragona BJ, Young KA, Dietz DM, Kabbaj M, Mazei-Robison M, Nestler EJ, and Wang ZX. Nucleus accumbens dopamine mediates amphetamine-induced impairment of social bonding in a monogamous rodent species. Proc Natl Acad Sci USA. 107(3):1217-1222. (2010) PDF
Stack A, Carrier N, Dietz D, Hollis F, Sorenson J, Kabbaj M. Sex differences in social interaction in rats: role of the immediate-early gene zif268. Neuropsychopharmacology. Jan;35(2):570-80. (2010)
Laplant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J, Warren BL, Maze I, Dietz DM, Watts EL, Iñiguez SD, Koo JW, Mouzon E, Renthal W, Hollis F, Wang H, Noonan MA, Ren Y, Eisch AJ, Bolaños CA, Kabbaj M, Xiao G, Neve RL, Hurd YL, Oosting RS, Fan G, Morrison JH, Nestler EJ. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci. 13(9), 1137-1143. (2010). (2010)
Hollis F, Wang H, Dietz D, Gunjan A and Kabbaj M. The effects of repeated social defeat on long -term depressive-like behavior and short-term histone modifications in the hippocampus in male Sprague Dawley rats. Psychopharmacology (Berl). 211:69-77. (2010)
LaPlant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J, Warren BL, Maze I, Dietz DM, Watts EL, Iñiguez SD, Koo JW, Mouzon E, Renthal W, Hollis F, Wang H, Noonan MA, Ren Y, Eisch AJ, Bolaños CA, Kabbaj M, Xiao G, Neve RL, Hurd YL, Oosting RS, Fan G, Morrison JH, Nestler EJ. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nature Neuroscience. 13(9):1137-43. (2010)
Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ. Genome Wide Promoter Analysis of Histone Modifications induced by Cocaine. Neuron. 62(3):335-48. (2009)
Dietz DM, Dietz KC, Moore S, Ouimet CC, Kabbaj M. Repeated social defeat stress-induced sensitization to the locomotor activating effects of d-amphetamine: role of individual differences. Psychopharmacology (Berl). 198(1):51-62. (2008)
Kabbaj M, Isgor C. Effects of chronic environmental and social stimuli during adolescence on mesolimbic dopaminergic circuitry markers. Neurosci Lett. 422(1):7-12. (2007)
Kabbaj M, Morley-Fletcher S, Le Moal M, Maccari S. Individual differences in the effects of chronic prazosin hydrochloride treatment on hippocampal mineralocorticoid and glucocorticoid receptors. Eur J Neurosci. 25(11):3312-8. (2007)
Dietz D, Wang H, Kabbaj M. Corticosterone fails to produce conditioned place preference or conditioned place aversion in rats. Behav Brain Res. 181(2):287-91. (2007)
Clinton SM, Vázquez DM, Kabbaj M, Kabbaj MH, Watson SJ, Akil H. Individual differences in novelty-seeking and emotional reactivity correlate with variation in maternal behavior. Horm Behav. 51(5):655-64. (2007)
Kabbaj M. Individual differences in vulnerability to drug abuse: the high responders/low responders model. CNS Neurol Disord Drug Targets. 5(5):513-20. (2006)
Dietz DM, Tapocik J, Gaval-Cruz M, Kabbaj M. Dopamine transporter, but not tyrosine hydroxylase, may be implicated in determining individual differences in behavioral sensitization to amphetamine. Physiol Behav. 86(3):347-55. (2005)
Kabbaj M, Evans S, Watson SJ, Akil H. The search for the neurobiological basis of vulnerability to drug abuse: using microarrays to investigate the role of stress and individual differences. Neuropharmacology. 47 Suppl 1:111-22. (2004)
Isgor C, Kabbaj M, Akil H, Watson SJ. Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats. Hippocampus. 14(5):636-48. (2004)
Kabbaj M. Neurobiological bases of individual differences in emotional and stress responsiveness: high responders-low responders model. Arch Neurol. 61(7):1009-12. (2004)
Neal CR Jr, Weidemann G, Kabbaj M, Vázquez DM. Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat. Am J Physiol Regul Integr Comp Physiol. 287(2):R375-85. (2004)
Kabbaj M , Yoshida S, Numachi Y , Sato M, Devine D.P and Matsuoka H. Metamphetamine differentially regulates hippocampal glucocorticoids and mineralocorticoids receptors mRNA in Fischer and Lewis rats . Molecular Brain Research. 117(1):8-14. (2003)
C. Isgor; M. Cecchi; Kabbaj M; H. Akil and S.J. . Watson Estrogen Receptor B in the Paraventricular Nucleus of Hypothalamus Regulates the Neuroendocrine Response to Stress and is regulated by Corticosterone. . Neurosciences. 121:837–845. (2003)
Kabbaj M *, C. Isgor, S. J. Watson, H. Akil . Stress during Adolescence Alters Behavioral Sensitization to Amphetamine.. Neuroscience. 113 (2): 395-400. (2002)
Evans SJ, Datson N, Kabbaj M, Thompson RC, Vreugdenhil, DeKloet ER, Watson SJ and Akil H. Evaluation of Affymetrix Gene Chip Sensitivity in rat hippocampal tissue using SAGE analysis. . European Journal of Neuroscience. 16(3):409-413. (2002)
Lu XY, Shieh KR, Kabbaj M, Barsh GS, Akil H and Watson S.J. . Diurnal Rhythm of Agouti-Related Protein and Its Relation to Corticosterone and Food Intake.. Endocrinology. 143 (10): 3905-3915. (2002)
Kabbaj M and Akil H . Individual differences in Novelty-Seeking Behavior in rats: a cfos study. Neurosciences. 106 (3): 535-545. (2001)
Kabbaj M, C.S. Norton, S. Kollack-Walker, T. E. Robinson, S.J. Watson and H. Akil1. Social Defeat alters the acquisition of cocaine self-administration in rats: role of Individual Differences in cocaine taking-behavior. . Psychopharmacology. 158 (4): 382-387. (2001)
Kabbaj M, Devine D.P, Savage V and Akil H . Neurobiological Correlates of Individual Differences in Novelty-Seeking Behavior in the Rat: Differential Expression of Stress-Related Molecules.. Journal of Neuroscience. 20: 6983-6988. (2000)
Maccari S, Barbazanges A, Kabbaj M, Piazza PV and M Le Moal . Long-term influences of perinatal life events on the behavioral and biological responses to stimuli: role of the mother. . 40 th. OHOLO conference on New Frontiers in Stress Research: Modulation of Brain Function, Harwood Academic publisher gmbh, Amsterdam. 141-154. (1997)
Kabbaj M, Le Moal M and Maccari S . Hippocampal type I and type II corticosteroid receptors are differentially regulated by chronic prazosin treatment. . Neuroscience. 73: 963-970. (1996)
Kabbaj M, Piazza PV, Simon H, Le Moal M and Maccari S . Opposite effects on hippocampal corticosteroid receptors induced by stimulation of beta and alpha-1 noradrenergic receptors. . Neuroscience. 66: 539-545. (1995)
Maccari S, Piazza PV, Kabbaj M, Barbazanges A, Simon H and Le Moal M . Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress. . Journal of Neuroscience. 15: 110-116. (1995)
Casolini P, Kabbaj M, Piazza PV, Angelucci L, Simon H, Le Moal M and Maccari S . The D1 dopamine agonist SKF 38393, but not the D2 agonist LY 171555 decrease the affinity of type II corticosteroid receptors in rat hippocampus and ventral striatum.. Neuroscience. 60: 939-943. (1994)
Henry C, Kabbaj M, Simon H, Le Moal M and Maccai S . Prenatal stress increases the hypothalamo-pituitary-adrenal axis response in young and adult rats.. J Neuroendocrinol.. 6: 341-345. (1994)
Casolini P, Piazza PV, Kabbaj M, Leprat F, Angelucci L, Simon H, Le Moal M and Maccari S. The mesolimbic dopaminergic system exerts an inhibitory influence on brain corticosteroid receptor affinities.. Neuroscience. 55: 429-434. (1993)
Casolini P, Kabbaj M, Leprat F, Piazza PV, Rouge-Pont F, Angelucci L, Simon H, Le Moal M and Maccari S . Basal and stress-induced corticosterone secretion is decreased by lesion of mesencephalic dopaminergic neurons.. Brain Research. 622: 311-314. (1993)
Wang H, Duclot F, Liu Y, Wang Z and Kabbaj M. Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles.. Nature Neuroscience. 16 (7): 919-924.