Professor of Pharmacology and Toxicology
Neurobiology, Drug Development for Impulse-Control and Neurodevelopmental Problems
My research is primarily focused on the characterization of the biological bases of impulse-control disorders (pathological aggression, gambling) and neurodevelopmental disorders (Tourette syndrome and autism-spectrum disorder) through the employment of behavioral tests in animal models. In particular, my key scientific interest is the identification of the mechanisms of interaction between lipid mediators (including neuroactive steroids and endocannabinoids) and key brain neurotransmitters, such as dopamine and serotonin. To this end, we employ a broad array of behavioral, biochemical and molecular biological techniques, as well as stereotactic surgery and HPLC.
My laboratory is currently involved in two major translational research projects. The first target of our investigations is the characterization of the molecular substrates of gene x environment interactions in impulsive aggression. The second aim of our research is the development of novel steroid- and cannabinoid-based tools for the therapy of impulse-control disorders, Tourette syndrome, and mood disorders. Both projects involve multiple collaborations with several basic and clinical scientists in US, Canada, Italy, France, Spain, and Germany.
References (Selected Publications)
- Devoto P, Frau R, Bini V, Pillolla G, Saba P, Flore G, Corona M, Marrosu F, Bortolato M. Inhibition of 5α-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation. Psychoneuroendocrinology. 2012 Oct;37(10):1630-45.
- Yardley MM, Wyatt L, Khoja S, Asatryan L, Ramaker MJ, Finn DA, Alkana RL, Huynh N, Louie SG, Petasis NA, Bortolato M, Davies DL. Ivermectin reduces alcohol intake and preference in mice. Neuropharmacology. 2012 Aug;63(2):190-201.
- Bortolato M, Cannas A, Solla P, Bini V, Puligheddu M, Marrosu F. Finasteride attenuates pathological gambling in patients with Parkinson disease. J Clin Psychopharmacol. 2012 Jun;32(3):424-5.
- Bortolato M, Godar SC, Melis M, Soggiu A, Roncada P, Casu A, Flore G, Chen K, Frau R, Urbani A, Castelli MP, Devoto P, Shih JC. NMDARs mediate the role of monoamine oxidase A in pathological aggression. J Neurosci. 2012 Jun 20;32(25):8574-82.
- Castelli MP, Casti A, Casu A, Frau R, Bortolato M, Spiga S, Ennas MG. Regional distribution of 5α-reductase type 2 in the adult rat brain: An immunohistochemical analysis. Psychoneuroendocrinology. 2013 Feb;38(2):281-93.
- Bortolato M, Godar SC, Alzghoul L, Zhang J, Darling RD, Simpson KL, Bini V, Chen K, Wellman CL, Lin RC, Shih JC. Monoamine oxidase A and A/B knockout mice display autistic-like features. Int J Neuropsychopharmacol. 2013 May;16(4):869-88.
- Frau R, Pillolla G, Bini V, Tambaro S, Devoto P, Bortolato M. Inhibition of 5α-reductase attenuates behavioral effects of D(1)-, but not D(2)-like receptor agonists in C57BL/6 mice. Psychoneuroendocrinology. 2013 Apr;38(4):542-51.
- Bortolato M, Yardley MM, Khoja S, Godar SC, Asatryan L, Finn DA, Alkana RL, Louie SG, Davies DL. Pharmacological insights into the role of P2X4 receptors in behavioural regulation: lessons from ivermectin. Int J Neuropsychopharmacol. 2013 Jun;16(5):1059-70.
- Bortolato M, Pivac N, Muck Seler D, Nikolac Perkovic M, Pessia M, Di Giovanni G. The role of the serotonergic system at the interface of aggression and suicide. Neuroscience 2013 Apr 16;236: 160-85.
- Tambaro S, Tomasi ML, Bortolato M. Long-term CB1 receptor blockade enhances vulnerability to anxiogenic-like effects of cannabinoids. 2013 Jul;70:268-77
- Wyatt LR, Godar SC, Khoja S, Jakowec MW, Alkana RL, Bortolato M, Davies DL. Socio-communicative and sensorimotor impairments in male P2X4-deficient mice. 2013 Sep;38(10):1993-2002.
- Davis DA*, Bortolato M*, Godar SC, Sander TK, Iwata N, Pakbin P, Shih JC, Berhane K, McConnell R, Sioutas C, Finch CE, Morgan TE. Prenatal exposure to urban air nanoparticulate in mice causes neuronal differentiation and depression-like responses. PLoS One. 2013 May 29;8(5):e64128.
- Bortolato M, Frau R, Godar SC, Mosher LJ, Paba S, Marrosu F, Devoto P. The implication of neuroactive steroids in tourette's syndrome pathogenesis: a role for 5α-reductase? J Neuroendocrinol. 2013 Nov;25(11):1196-208.
- Singh C, Bortolato M, Bali N, Godar SC, Scott AL, Chen K, Thompson RF, Shih JC. Cognitive abnormalities and hippocampal alterations in monoamine oxidase A and B knockout mice. Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12816-21.
- Bortolato M, Godar SC, Tambaro S, Li FG, Devoto P, Coba MP, Chen K, Shih JC. Early postnatal inhibition of serotonin synthesis results in long-term reductions of perseverative behaviors, but not aggression, in MAO A-deficient mice. Neuropharmacology. 2013 Dec;75:223-32.
- Frau R, Bini V, Pes R, Pillolla G, Saba P, Devoto P, Bortolato M. Inhibition of 17α-hydroxylase/C17,20 lyase reduces gating deficits consequent to dopaminergic activation. Psychoneuroendocrinology. 2014 Jan;39:204-13.
- Godar SC, Bortolato M. Gene-sex interactions in schizophrenia: focus on dopamine neurotransmission. Front Behav Neurosci. 2014 Mar 6;8:71
- Bortolato M, Bini V, Frau R, Devoto P, Pardu A, Fan Y, Solbrig MV. Juvenile cannabinoid treatment induces frontostriatal gliogenesis in Lewis rats. Eur Neuropsychopharmacol. 2014 Jun;24(6):974-85.
- Frau R, Bini V, Pillolla G, Malherbe P, Pardu A, Thomas AW, Devoto P, Bortolato M. Positive Allosteric Modulation of GABA(B) Receptors Ameliorates Sensorimotor Gating in Rodent Models. CNS Neurosci Ther. 2014 Jul;20(7):679-84.
- Godar SC, Bortolato M, Castelli MP, Casti A, Casu A, Chen K, Ennas MG, Tambaro S, Shih JC. The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake. J Psychiatr Res. 2014 Sep;56:1-9.
- Stetler DA, Davis C, Leavitt K, Schriger I, Benson K, Bhakta S, Wang LC, Oben C, Watters M, Haghnegahdar T, Bortolato M. Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders. J Psychiatr Res. 2014 Nov;58:69-75
- Godar SC, Bortolato M, Richards SE, Li FG, Chen K, Wellman CL, Shih JC. Monoamine oxidase A is required for rapid dendritic remodeling in response to stress. Int J Neuropsychopharmacol, 2015 Apr 8;18(9).
- Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M. Adverse Effects of 5α-Reductase Inhibitors: What do we know, Don't Know, and Need to Know? Rev Endocr Metab Disord, 2015 Sep;16(3):177-98.
- Frau R, Abbiati F, Bini V, Casti A, Caruso D, Devoto P, Bortolato M. Targeting neurosteroid synthesis as a therapy for schizophrenia-related alterations induced by early psychosocial stress. Schizophrenia Res, 2015 Nov;168(3):640-8.
- Moskovitz J, Walss-Bass C, Cruz DA, Thompson PM, Hairston J, Bortolato M. The enzymatic activities of brain COMT and methionine sulfoxide reductase are correlated in a COMT Val/Met allele-dependent fashion. Neuropath Appl Neurobiol, 2015 Dec;41(7):941-51.
- Frau R, Mosher LJ, Bini V, Pillolla G, Pes R, Saba P, Fanni S, Devoto P, Bortolato M. The neurosteroidogenic enzyme 5α-reductase modulates the role of D1 dopamine receptors in rat sensorimotor gating. Psychoneuroendocrinology, 2016 Jan;63:59-67.
- Godar SC, Mosher LJ, Strathman HJ, Gochi AM, Jones CM, Fowler SC, Bortolato M. The D1CT-7 mouse model of Tourette syndrome displays sensorimotor gating deficits in response to spatial confinement. Br J Pharmacol, 2016 Jul; 173(13):2111-21.
- Mosher LJ, Frau R, Pardu A, Pes R, Devoto P, Bortolato M. Selective activation of D1 dopamine receptors impairs sensorimotor gating in Long-Evans rats. Br J Pharmacol, 2016 Jul; 173(13):2122-34.
- Godar SC, Fite PJ, McFarlin KM, Bortolato M. The role of monoamine oxidase A in aggression: Current translational developments and future challenges. Prog Neuropsychopharmacol Biol Psychiatry, 2016 Aug 1; 69:90-100.
- Soggiu A, Piras C, Greco V, Devoto P, Urbani A, Calzetta L, Bortolato M, Roncada P. Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens. Psychoneuroendocrinology, 2016 Dec;74:387-396.
- Pes R, Godar SC, Fox AT, Burgeno LM, Strathman HJ, Jarmolowicz DP, Devoto P, Levant B, Phillips PE, Fowler SC, Bortolato M. Pramipexole enhances disadvantageous decision-making: lack of relation to changes in phasic dopamine release. Neuropharmacology, 2017 Mar 1;114:77-87.
- Godar SC, Bortolato M. What makes you tic? Translational approaches to study the role of stress and contextual triggers in Tourette syndrome, Neurosci Biobehav Rev, 2017 May;76(Pt A):123-133.
- Frau R, Bini V, Soggiu A, Scheggi S, Pardu A, Fanni S, Roncada P, Puligheddu M, Marrosu F, Caruso D, Devoto P, Bortolato M. The neurosteroidogenic enzyme 5α-reductase mediates psychotic-like complications of sleep deprivation. Neurosychopharmacology, in press
- Frau R, Savoia P, Fanni S, Fiorentini C, Fidalgo C, Tronci E, Stancampiano R, Meloni M, Cannas A, Marrosu F, Bortolato M, Devoto P, Missale C, Carta M. The 5-alpha reductase inhibitor finasteride reduces dyskinesia in a rat model of Parkinson’s disease. Exp Neurol, in press
- Mosher LJ, Godar SC, Nelson M, Fowler SC, Pinna G, Bortolato M. Allopregnanolone mediates the exacerbation of Tourette-like responses by acute stress in mouse models. Sci Rep, Jun 13;7(1):3348.