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David Dominguez Aguilar, Ph.D.

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The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. F31MH105166 (AGUILAR, DAVID DOMINGUEZ) May 1, 2015 - Apr 30, 2017
    NIH/NIMH
    Adolescent cannabinoid exposure in a rodent model of schizophrenia susceptibility
    Role: Principal Investigator
  2. 1F31MH105166 (Aguilar) May 1, 2015 - May 20, 2016
    NIH/NIMH
    Adolescent Cannabinoid Exposure in a Rodent Model of Schizophrenia Susceptibility
    Role Description: This project aims to explore the interaction of genetic and environmental factors in the development of psychotic symptoms. Cannabinoid exposure during adolescence is associated with an increased risk of developing schizophrenia, but this correlation is not causative. Thus, it is likely that people with a genetic predisposition to psychotic symptoms are more strongly affected by environmental risk factors. We have developed an animal model with increased susceptibility to schizophrenia-like symptoms by using the second filial (F2) generation of rats that were developmentally disrupted with methylazoxymethanol acetate (MAM). We hypothesize cannabinoid exposure during adolescence will increase the proportion of these "F2 MAM" rats displaying a schizophrenia-like phenotype. This phenotype will be evaluated at the behavioral level (with stimulant-induced hyperlocomotion, social interaction, and attentional set-shifting), the cellular level (spontaneous dopamine neuron activity and hippocampal pyramidal activity), and the molecular level (expression of inhibitory markers). Understanding additive or interactive effects of risk factors could allow us to make more accurate predictions of developing psychotic symptoms, as well as personalize warnings for those already at risk. Furthermore, a model of susceptibility would be extremely useful for preventative experimental therapies. This proposal will provide important training in experimental design, laboratory and analytical techniques, ethics, and other essential skills for a future independent investigator.
    Role: PI

Bibliographic
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  1. Uygun DS, Katsuki F, Bolortuya Y, Aguilar DD, McKenna JT, Thankachan S, McCarley RW, Basheer R, Brown RE, Strecker RE, McNally JM. Validation of an automated sleep spindle detection method for mouse electroencephalography. Sleep. 2019 Feb 01; 42(2). PMID: 30476300.
    Citations:    Fields:    
  2. Perez SM, Donegan JJ, Boley AM, Aguilar DD, Giuffrida A, Lodge DJ. Ventral hippocampal overexpression of Cannabinoid Receptor Interacting Protein 1 (CNRIP1) produces a schizophrenia-like phenotype in the rat. Schizophr Res. 2019 Apr; 206:263-270. PMID: 30522798.
    Citations:    Fields:    
  3. Aguilar DD, Giuffrida A, Lodge DJ. Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine Neuron Activity in a Rodent Model of Schizophrenia Susceptibility. Int J Neuropsychopharmacol. 2018 04 01; 21(4):393-403. PMID: 29329382.
    Citations:    Fields:    
  4. Flannick J, Fuchsberger C, Mahajan A, Teslovich TM, Agarwala V, Gaulton KJ, Caulkins L, Koesterer R, Ma C, Moutsianas L, McCarthy DJ, Rivas MA, Perry JRB, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, Müller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SCJ, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MCY, Palmer ND, Balkau B, Stancáková A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JMM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VKL, Park KS, Saleheen D, So WY, Tam CHT, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler SP, Freedman BI, Griswold M, Hale DE, Hicks PJ, Khor CC, Kumar S, Lehne B, Thuillier D, Lim WY, Liu J, Loh M, Musani SK, Puppala S, Scott WR, Yengo L, Tan ST, Taylor HA, Thameem F, Wilson G, Wong TY, Njølstad PR, Levy JC, Mangino M, Bonnycastle LL, Schwarzmayr T, Fadista J, Surdulescu GL, Herder C, Groves CJ, Wieland T, Bork-Jensen J, Brandslund I, Christensen C, Koistinen HA, Doney ASF, Kinnunen L, Esko T, Farmer AJ, Hakaste L, Hodgkiss D, Kravic J, Lyssenko V, Hollensted M, Jørgensen ME, Jørgensen T, Ladenvall C, Justesen JM, Käräjämäki A, Kriebel J, Rathmann W, Lannfelt L, Lauritzen T, Narisu N, Linneberg A, Melander O, Milani L, Neville M, Orho-Melander M, Qi L, Qi Q, Roden M, Rolandsson O, Swift A, Rosengren AH, Stirrups K, Wood AR, Mihailov E, Blancher C, Carneiro MO, Maguire J, Poplin R, Shakir K, Fennell T, DePristo M, de Angelis MH, Deloukas P, Gjesing AP, Jun G, Nilsson P, Murphy J, Onofrio R, Thorand B, Hansen T, Meisinger C, Hu FB, Isomaa B, Karpe F, Liang L, Peters A, Huth C, O'Rahilly SP, Palmer CNA, Pedersen O, Rauramaa R, Tuomilehto J, Salomaa V, Watanabe RM, Syvänen AC, Bergman RN, Bharadwaj D, Bottinger EP, Cho YS, Chandak GR, Chan JC, Chia KS, Daly MJ, Ebrahim SB, Langenberg C, Elliott P, Jablonski KA, Lehman DM, Jia W, Ma RCW, Pollin TI, Sandhu M, Tandon N, Froguel P, Barroso I, Teo YY, Zeggini E, Loos RJF, Small KS, Ried JS, DeFronzo RA, Grallert H, Glaser B, Metspalu A, Wareham NJ, Walker M, Banks E, Gieger C, Ingelsson E, Im HK, Illig T, Franks PW, Buck G, Trakalo J, Buck D, Prokopenko I, Mägi R, Lind L, Farjoun Y, Owen KR, Gloyn AL, Strauch K, Tuomi T, Kooner JS, Lee JY, Park T, Donnelly P, Morris AD, Hattersley AT, Bowden DW, Collins FS, Atzmon G, Chambers JC, Spector TD, Laakso M, Strom TM, Bell GI, Blangero J, Duggirala R, Tai ES, McVean G, Hanis CL, Wilson JG, Seielstad M, Frayling TM, Meigs JB, Cox NJ, Sladek R, Lander ES, Gabriel S, Mohlke KL, Meitinger T, Groop L, Abecasis G, Scott LJ, Morris AP, Kang HM, Altshuler D, Burtt NP, Florez JC, Boehnke M, McCarthy MI. Sequence data and association statistics from 12,940 type 2 diabetes cases and controls. Sci Data. 2017 12 19; 4:170179. PMID: 29257133.
    Citations:    
  5. Manning A, Highland HM, Gasser J, Sim X, Tukiainen T, Fontanillas P, Grarup N, Rivas MA, Mahajan A, Locke AE, Cingolani P, Pers TH, Viñuela A, Brown AA, Wu Y, Flannick J, Fuchsberger C, Gamazon ER, Gaulton KJ, Im HK, Teslovich TM, Blackwell TW, Bork-Jensen J, Burtt NP, Chen Y, Green T, Hartl C, Kang HM, Kumar A, Ladenvall C, Ma C, Moutsianas L, Pearson RD, Perry JRB, Rayner NW, Robertson NR, Scott LJ, van de Bunt M, Eriksson JG, Jula A, Koskinen S, Lehtimäki T, Palotie A, Raitakari OT, Jacobs SBR, Wessel J, Chu AY, Scott RA, Goodarzi MO, Blancher C, Buck G, Buck D, Chines PS, Gabriel S, Gjesing AP, Groves CJ, Hollensted M, Huyghe JR, Jackson AU, Jun G, Justesen JM, Mangino M, Murphy J, Neville M, Onofrio R, Small KS, Stringham HM, Trakalo J, Banks E, Carey J, Carneiro MO, DePristo M, Farjoun Y, Fennell T, Goldstein JI, Grant G, Hrabé de Angelis M, Maguire J, Neale BM, Poplin R, Purcell S, Schwarzmayr T, Shakir K, Smith JD, Strom TM, Wieland T, Lindstrom J, Brandslund I, Christensen C, Surdulescu GL, Lakka TA, Doney ASF, Nilsson P, Wareham NJ, Langenberg C, Varga TV, Franks PW, Rolandsson O, Rosengren AH, Farook VS, Thameem F, Puppala S, Kumar S, Lehman DM, Jenkinson CP, Curran JE, Hale DE, Fowler SP, Arya R, DeFronzo RA, Abboud HE, Syvänen AC, Hicks PJ, Palmer ND, Ng MCY, Bowden DW, Freedman BI, Esko T, Mägi R, Milani L, Mihailov E, Metspalu A, Narisu N, Kinnunen L, Bonnycastle LL, Swift A, Pasko D, Wood AR, Fadista J, Pollin TI, Barzilai N, Atzmon G, Glaser B, Thorand B, Strauch K, Peters A, Roden M, Müller-Nurasyid M, Liang L, Kriebel J, Illig T, Grallert H, Gieger C, Meisinger C, Lannfelt L, Musani SK, Griswold M, Taylor HA, Wilson G, Correa A, Oksa H, Scott WR, Afzal U, Tan ST, Loh M, Chambers JC, Sehmi J, Kooner JS, Lehne B, Cho YS, Lee JY, Han BG, Käräjämäki A, Qi Q, Qi L, Huang J, Hu FB, Melander O, Orho-Melander M, Below JE, Aguilar D, Wong TY, Liu J, Khor CC, Chia KS, Lim WY, Cheng CY, Chan E, Tai ES, Aung T, Linneberg A, Isomaa B, Meitinger T, Tuomi T, Hakaste L, Kravic J, Jørgensen ME, Lauritzen T, Deloukas P, Stirrups KE, Owen KR, Farmer AJ, Frayling TM, O'Rahilly SP, Walker M, Levy JC, Hodgkiss D, Hattersley AT, Kuulasmaa T, Stancáková A, Barroso I, Bharadwaj D, Chan J, Chandak GR, Daly MJ, Donnelly PJ, Ebrahim SB, Elliott P, Fingerlin T, Froguel P, Hu C, Jia W, Ma RCW, McVean G, Park T, Prabhakaran D, Sandhu M, Scott J, Sladek R, Tandon N, Teo YY, Zeggini E, Watanabe RM, Koistinen HA, Kesaniemi YA, Uusitupa M, Spector TD, Salomaa V, Rauramaa R, Palmer CNA, Prokopenko I, Morris AD, Bergman RN, Collins FS, Lind L, Ingelsson E, Tuomilehto J, Karpe F, Groop L, Jørgensen T, Hansen T, Pedersen O, Kuusisto J, Abecasis G, Bell GI, Blangero J, Cox NJ, Duggirala R, Seielstad M, Wilson JG, Dupuis J, Ripatti S, Hanis CL, Florez JC, Mohlke KL, Meigs JB, Laakso M, Morris AP, Boehnke M, Altshuler D, McCarthy MI, Gloyn AL, Lindgren CM. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes. 2017 07; 66(7):2019-2032. PMID: 28341696.
    Citations: 4     Fields:    Translation:Humans
  6. Aguilar DD, Giuffrida A, Lodge DJ. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia. J Psychopharmacol. 2016 Feb; 30(2):169-81. PMID: 26510449.
    Citations: 2     Fields:    Translation:AnimalsCells
  7. Perez SM, Aguilar DD, Neary JL, Carless MA, Giuffrida A, Lodge DJ. Schizophrenia-Like Phenotype Inherited by the F2 Generation of a Gestational Disruption Model of Schizophrenia. Neuropsychopharmacology. 2016 Jan; 41(2):477-86. PMID: 26068729.
    Citations: 1     Fields:    Translation:AnimalsCells
  8. Aguilar DD, Chen L, Lodge DJ. Increasing endocannabinoid levels in the ventral pallidum restore aberrant dopamine neuron activity in the subchronic PCP rodent model of schizophrenia. Int J Neuropsychopharmacol. 2014 Oct 31; 18(1). PMID: 25539511.
    Citations: 4     Fields:    Translation:AnimalsCells
  9. Seillier A, Dominguez Aguilar D, Giuffrida A. The dual FAAH/MAGL inhibitor JZL195 has enhanced effects on endocannabinoid transmission and motor behavior in rats as compared to those of the MAGL inhibitor JZL184. Pharmacol Biochem Behav. 2014 Sep; 124:153-9. PMID: 24911644.
    Citations: 7     Fields:    Translation:Animals
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.