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Evolution of the HIV-1 transgenic rat: utility in assessing the progression of HIV-1-associated neurocognitive disorders

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Abstract

Understanding the progression of HIV-1-associated neurocognitive disorders (HAND) is a critical need as the prevalence of HIV-1 in older individuals (>50 years) is markedly increasing due to the great success of combination antiretroviral therapy (cART). Longitudinal experimental designs, in comparison to cross-sectional studies, provide an opportunity to establish age-related disease progression in HAND. The HIV-1 transgenic (Tg) rat, which has been promoted for investigating the effect of long-term HIV-1 viral protein exposure, was used to examine two interrelated goals. First, to establish the integrity of sensory and motor systems through the majority of the animal’s functional lifespan. Strong evidence for intact sensory and motor system function through advancing age in HIV-1 Tg and control animals was observed in cross-modal prepulse inhibition (PPI) and locomotor activity. The integrity of sensory and motor system function suggested the utility of the HIV-1 Tg rat in investigating the progression of HAND. Second, to assess the progression of neurocognitive impairment, including temporal processing and long-term episodic memory, in the HIV-1 Tg rat; the factor of biological sex was integral to the experimental design. Cross-modal PPI revealed significant alterations in the development of temporal processing in HIV-1 Tg animals relative to controls; alterations which were more pronounced in female HIV-1 Tg rats relative to male HIV-1 Tg rats. Locomotor activity revealed deficits in intrasession habituation, suggestive of a disruption in long-term episodic memory, in HIV-1 Tg animals. Understanding the progression of HAND heralds an opportunity for the development of an advantageous model of progressive neurocognitive deficits in HIV-1 and establishes fundamental groundwork for the development of neurorestorative treatments.

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References

  • Abbondanzo SJ, Chang SL (2014) HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging. PLoS One 9:e105256. doi:10.1371/journal.pone.0105256

    Article  PubMed  PubMed Central  Google Scholar 

  • Barker GRI, Bird F, Alexander V, Warburton EC (2007) Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci 27:2948–2957. doi:10.1523/JNEUROSCI.5289-06.2007

    Article  CAS  PubMed  Google Scholar 

  • Bertrand SJ, Mactutus CF, Harrod SB, Morgan AJ, Booze RM (2013) HIV-1 transgenic rat: altered internal motivational state for natural rewards [abstract]. J Neurovirol 19:S12

    Google Scholar 

  • Bethus I, Tse D, Morris RG (2010) Dopamine and memory: modulation of the persistence of memory for novel hippocampal NMDA receptor-dependent paired associates. J Neurosci 30:1610–1618. doi:10.1523/JNEUROSCI.2721-09.2010

    Article  CAS  PubMed  Google Scholar 

  • Booze RM, Mactutus CF (1990) Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats. Experientia 46:292–297

    Article  CAS  PubMed  Google Scholar 

  • Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normal and schizophrenics. Psychophysiology 15:339–343. doi:10.1111/j.1469-8986.1978.tb01390.x

    Article  CAS  PubMed  Google Scholar 

  • Carlsson SG (1972) Effects of apomorphine on exploration. Physiol Behav 9:127–129

    Article  CAS  PubMed  Google Scholar 

  • Chang SL, Vigorito M (2006) Role of HIV-1 infection in addictive behavior: a study of the HIV-1 transgenic rat model. Am J Infect Diseases 2:98–106

    Article  CAS  Google Scholar 

  • Chao OY, Huston JP, Li JS, Wang AL, de Souza Silva MA (2016) The medial prefrontal cortex—lateral entorhinal cortex circuit is essential for episodic-like memory and associative object-recognition. Hippocampus 26:633–645. doi:10.1002/hipo.22547

    Article  PubMed  Google Scholar 

  • Coleman PD (2004) How old is old? Editorial Neurobiol Aging 25:1 Original work published 1989

    Article  PubMed  Google Scholar 

  • Crofton KM, Sheets LP (1989) Evaluation of sensory system function using reflex modification of the startle response. J Am Coll Toxicol 8:199–211

    Article  Google Scholar 

  • Denenberg VH (1984) Some statistical and experimental considerations in the use of the analysis-of-variance procedure. Am J Physiol-Reg I 246:R403–R408

    CAS  Google Scholar 

  • Eacott MJ, Easton A, Zinkivskay A (2005) Recollection in an episodic-like memory task in the rat. Learn Mem 12:221–223. doi:10.1101/lm.92505

    Article  PubMed  Google Scholar 

  • Ellenbroek BA, Budde S, Cools AR (1996) Prepulse inhibition and latent inhibition: the role of dopamine in the medial prefrontal cortex. Neuroscience 75:535–542

    Article  CAS  PubMed  Google Scholar 

  • Fazeli PL, Crowe M, Ross LA, Wadley V, Ball K, Vance DE (2014) Cognitive functioning in adults aging with HIV: a cross-sectional analysis of cognitive subtypes and influential factors. J Clin Res HIV AIDS Prev 1:155–169. doi:10.14302/issn.2324-7339.jcrhap-13-191

    Article  PubMed  PubMed Central  Google Scholar 

  • Fendt M, Koch M, Schnitzler HU (1994) Sensorimotor gating deficit after lesions of the superior colliculus. Neuroreport 5:1725–1738

    Article  CAS  PubMed  Google Scholar 

  • Ferré S, Fuxe K, von Euler G, Johansson B, Fredholm BB (1992) Adenosine-dopamine interactions in the brain. Neuroscience 51:501–512

    Article  PubMed  Google Scholar 

  • Fitting S, Booze RM, Mactutus CF (2006) Neonatal intrahippocampal glycoprotein 120 injection: the role of dopaminergic alterations in prepulse inhibition in adult rats. J Pharmacol Exp Ther 318:1352–1358. doi:10.1124/jpet.106.105742

    Article  CAS  PubMed  Google Scholar 

  • Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117–154

    Article  CAS  PubMed  Google Scholar 

  • Giros B, Jaber M, Jones SR, Wightman RM, Caron MG (1996) Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612. doi:10.1038/379606a0

    Article  CAS  PubMed  Google Scholar 

  • Greenhouse SW, Geisser S (1959) On methods in the analysis of profile data. Psychometrika 24:95–112

    Article  Google Scholar 

  • Harris JD (1943) Habituatory response decrement in the intact organism. Psychol Bull 40:385–422

    Article  Google Scholar 

  • Hauber W, Koch M (1997) Adenosine A2a receptors in the nucleus accumbens modulate prepulse inhibition of the startle response. Neuroreport 8:1515–1518

    Article  CAS  PubMed  Google Scholar 

  • Heaton RK, Clifford DB, Franklin DR, Woods SP, Ake C, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Rivera-Mindt M, Vigil OR, Taylor MJ, Collier AC, Marra CM, Gelman BB, JC MA, Morgello S, Simpson DM, JA MC, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, CHARTER Group (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy CHARTER study. Neurology 75:2087–2096. doi:10.1212/WNL.0b013e318200d727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heaton RK, Franklin DR, Ellis RJ, McCutchan JA, Letendre SL, Leblanc S, Corkran SH, Duarte NA, Clifford DB, Woods SP, Collier AC, Marra CM, Morgello S, Mindt MR, Taylor MJ, Marcotte TD, Atkinson JH, Wolfson T, Gelman BB, McArthur JC, Simpson DM, Abramson I, Gamst A, Fennema-Notestine C, Jernigan TL, Wong J, Grant I, CHARTER Group, HNRC Group (2011) HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 17:3–16. doi:10.1007/s13365-010-0006-1

    Article  CAS  PubMed  Google Scholar 

  • Hoffman HS, Ison JR (1980) Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input. Psychol Rev 87:175–189

    Article  CAS  PubMed  Google Scholar 

  • Ison JR, Hammond GR (1971) Modification of startle reflex in rat by changes in auditory and visual environments. J Comp Physiol Psychol 75:435–452

    Article  CAS  PubMed  Google Scholar 

  • Ison JR (1984) Reflex modification as an objective test for sensory processing following toxicant exposure. Neurobehav Toxicol Teratol 6:437–445

    CAS  PubMed  Google Scholar 

  • June HL, Yang ARST, Bryant JL, Jones O, Royal W (2009) Vitamin A deficiency and behavioral and motor deficits in the HIV-1 transgenic rat. J Neurovirol 15(5–6):380–389. doi:10.3109/13550280903350200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koch M (1999) The neurobiology of startle. Prog Neurobiol 59:107–128

    Article  CAS  PubMed  Google Scholar 

  • Kraemer HC, Yesavage JA, Taylor JL, Kupfer D (2000) How can be learn about developmental processes from cross-sectional studies, or can we? Am J Psychiatry 157:163–171. doi:10.1176/appi.ajp.157.2.163

    Article  CAS  PubMed  Google Scholar 

  • Lashomb AL, Vigorito M, Chang SL (2009) Further characterization of the spatial learning deficit in the human immunodeficiency virus-1 transgenic rat. J Neurovirol 15(1):14–24. doi:10.1080/13550280802232996

    Article  CAS  PubMed  Google Scholar 

  • Lee DE, Reid WC, Ibrahim WG, Peterson KL, Lentz MR, Maric D, Choyke PL, Jagoda EM, Hammoud DA (2014) Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV. Mol Imaging 13:1–10. doi:10.2310/7290.2014.00031

    PubMed  Google Scholar 

  • Leitner DS, Cohen ME (1985) Role of the interior colliculus in the inhibition of acoustic startle in the rat. Physiol Behav 34:65–70

    Article  CAS  PubMed  Google Scholar 

  • Letendre SL, Ellis RJ, Ances BM, McCutchan JA (2010) Neurologic complications of HIV disease and their treatment. Top HIV Med 18:45–55

    PubMed  PubMed Central  Google Scholar 

  • Leussis MP, Bolivar VJ (2006) Habituation in rodents: a review of behavior, neurobiology, and genetics. Neurosci Biobehav Rev 30:1045–1064. doi:10.1016/j.neubiorev.2006.03.006

    Article  PubMed  Google Scholar 

  • Li L, Priebe PM, Yeomans JS (1998) Prepulse inhibition of acoustic or trigeminal startle of rats by unilateral electrical stimulation of the inferior colliculus. Behav Neurosci 112:1187–1198

    Article  CAS  PubMed  Google Scholar 

  • Li L, Yeomans JS (2000) Using intracranial electrical stimulation to study the timing of prepulse inhibition of the startle reflex. Brain Res Protocol 5:67–74

    Article  CAS  Google Scholar 

  • Lisman JE, Grace AA (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron 46:703–713. doi:10.1016/j.neuron.2005.05.002

    Article  CAS  PubMed  Google Scholar 

  • Maki PM, Martin-Thormeyer E (2009) HIV, cognition and women. Neuropsychol Rev 19:204–214. doi:10.1007/s11065-009-9093-2

    Article  PubMed  PubMed Central  Google Scholar 

  • Maki PM, Rubin LH, Valcour V, Martin E, Crystal H, Young M, Weber KM, Manly J, Richardson J, Alden C, Anastos K (2015) Cognitive function in women with HIV: findings from the Women’s Interagency HIV Study. Neurology 84:231–240. doi:10.1212/WNL.0000000000001151

    Article  PubMed  PubMed Central  Google Scholar 

  • Mansbach RS, Geyer MA, Braff DL (1998) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–514

    Article  Google Scholar 

  • McArthur JC, Steiner J, Sacktor N, Nath A (2010) Human immunodeficiency virus-associated neurocognitive disorders: mind the gap. Ann Neurol 67:699–714. doi:10.1002/ana.22053

    CAS  PubMed  Google Scholar 

  • McGaughy J, Sarter M (1995) Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands. Psychopharmacology 117:340–357

    Article  CAS  PubMed  Google Scholar 

  • McLaurin KA, Booze RM, Mactutus CF (2016) Progression of temporal processing deficits in the HIV-1 transgenic rat. Sci Rep 6:32831. doi:10.1038/srep32831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McLaurin KA, Booze RM, Mactutus CF (2017a) Selective developmental alterations in the HIV-1 transgenic rat: opportunities for diagnosis of pediatric HIV-1. J Neurovirol 23(1):87–98. doi:10.1007/s13365-016-0476-x

  • McLaurin KA, Moran LM, Li H, Booze RM, Mactutus CF (2017b) A gap in time: extending our knowledge of temporal processing deficits in the HIV-1 transgenic rat. J NeuroImmune Pharmacol 12(1):171–179. doi:10.1007/s11481-016-9711-8

    Article  PubMed  Google Scholar 

  • McLaurin KA, Booze RM, Mactutus CF (2017c) Temporal processing demands in the HIV-1 transgenic rat: amodal gating and implications for diagnostics. Int J Dev Neurosci 57:12–20. doi:10.1016/j.ijdevneu.2016.11.004

    Article  PubMed  Google Scholar 

  • Moran LM, Aksenov MY, Booze RM, Webb KM, Mactutus CF (2012) Adolescent HIV-1 transgenic rats: evidence for dopaminergic alterations in behavior and neurochemistry revealed by methamphetamine challenge. Curr HIV-1 Res 10:415–424

    Article  CAS  Google Scholar 

  • Moran LM, Booze RM, Mactutus CF (2013a) Time and time again: temporal processing demands implicate perceptual and gating deficits in the HIV-1 transgenic rat. J NeuroImmune Pharmacol 8:988–997. doi:10.1007/s11481-013-9472-6

    Article  PubMed  PubMed Central  Google Scholar 

  • Moran LM, Booze RM, Webb KM, Mactutus CF (2013b) Neurobehavioral alterations in HIV-1 transgenic rats: evidence for dopaminergic dysfunction. Exp Neurol 239:139–147. doi:10.1016/j.expneurol.2012.10.008

    Article  CAS  PubMed  Google Scholar 

  • Moran LM, Booze RM, Mactutus CF (2014a) Modeling deficits in attention, inhibition, and flexibility in HAND. J NeuroImmune Pharmacol 9:508–521. doi:10.1007/s11481-014-9539-z

    Article  PubMed  PubMed Central  Google Scholar 

  • Moran LM, Fitting S, Booze RM, Webb KM, Mactutus CF (2014b) Neonatal intrahippocampal HIV-1 protein Tat(1-86) injection: neurobehavioral alterations in the absence of increase inflammatory cytokine activation. Int J Dev Neurosci 38:195–203. doi:10.1016/j.ijdevneu.2014.09.004

    Article  CAS  PubMed  Google Scholar 

  • Peng J, Vigorito M, Liu X, Zhou D, Wu X, Chang SL (2010) The HIV-1 transgenic rat as a model for HIV-1 infected individuals on HAART. J Neuroimmunol 218:94–101. doi:10.1016/j.jneuroim.2009.09.014

    Article  CAS  PubMed  Google Scholar 

  • Peris J, Coleman-Hardee M, Millard WJ (1992) Cocaine in utero enhances the behavioral response to cocaine in adult rats. Pharmacol Biochem Behav 42(3):509–515

    Article  CAS  PubMed  Google Scholar 

  • Pierce RC, Kalivas PW (2007) Locomotor behavior. Curr Protoc Neurosci:8.1.1–8.1.9. doi:10.1002/0471142301.ns0801s40

  • Rankin CH, Abrams T, Barry RJ, Bhatnagar S, Clayton D, Colombo J, Coppola G, Geyer MA, Glanzman DL, Marsland S, McSweeney F, Wilson DA, Wu C-F, Thompson RF (2009) Habituation revisited: an updated and revised description of the behavioral characteristics of habituation. Neurobiol Learn Mem 92:135–138. doi:10.1016/j.nlm.2008.09.012

    Article  PubMed  Google Scholar 

  • Reid W, Sadowska M, Denaro F, Rao S, Foulke J, Hayes N, Jones O, Doodnauth D, Davis H, Sill A, O’Driscoll P, Huso D, Fouts T, Lewis G, Hill M, Kamin-Lewis R, Wei C, Ray P, Gallo RC, Reitz M, Bryant J (2001) An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci U S A 98:9271–9276. doi:10.1073/pnas.161290298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid WC, Ibrahim WG, Kim SJ, Denaro F, Casas R, Lee DE, Maric D, Hammoud DA (2016a) Characterization of neuropathology in the HIV-1 transgenic rat at different ages. J Neuroimmunol 292:116–125. doi:10.1016/j.jneuroim.2016.01.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid WC, Casas R, Papadakis GZ, Muthusamy S, Lee DE, Ibrahim WG, Nair A, Koziol D, Maric D, Hammoud DA (2016b) Neurobehavioral abnormalities in the HIV-1 transgenic rat do not correspond to neuronal hypometabolism on 18F-FDG-PET. PLoS One 11:e0152265. doi:10.1371/journal.pone.0152265

    Article  PubMed  PubMed Central  Google Scholar 

  • Repunte-Canonigo V, Lefebvre C, George O, Kawamura T, Morales M, Koob GF, Califano A, Masliah E, Sanna PP (2014) Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats. Mol Neurodegener 9:26. doi:10.1186/1750-1326-9-26

    Article  PubMed  PubMed Central  Google Scholar 

  • Robbins TW (1977) A critique of the methods available for the measurement of spontaneous motor activity. In: Iversen LL, Iversen SD, Snyder SH (Eds) Handbook of psychopharmacology, Volume 7. Plenum Press, NY, pp 37–82.

  • Roscoe RF Jr, Mactutus CF, Booze RM (2014) HIV-1 transgenic female rat: synaptodendritic alterations of medium spiny neurons in the nucleus accumbens. J NeuroImmune Pharmacol 9:642–653. doi:10.1007/s11481-014-9555-z

    Article  PubMed  PubMed Central  Google Scholar 

  • Schwarzkopf SB, McCoy L, Smith DA, Boutros NN (1993) Test-retest reliability of prepulse inhibition of the acoustic startle response. Biol Psychiatry 34:896–900

    Article  CAS  PubMed  Google Scholar 

  • Sheppard DP, Iudicello JE, Bondi MW, Doyle KL, Morgan EE, Massman PJ, Gilbert PE, Woods SP (2015) Elevated rates of mild cognitive impairment in HIV disease. J Neurovirol 21:576–584. doi:10.1007/s13365-015-0366-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smit M, Binkman K, Geerlings S, Smit C, Thyagarajan K, Sighem AV, de Wolf F, Hallett TB, ATHENA observational cohort (2015) Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis 15:810–818. doi:10.1016/S1473-3099(15)00056-0

    Article  PubMed  PubMed Central  Google Scholar 

  • Swerdlow NR, Caine SB, Braff DL, Geyer MA (1992) The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications. J Psychopharmacol 6:176–190. doi:10.1177/026988119200600210

    Article  CAS  PubMed  Google Scholar 

  • Taber MT, Fibiger HC (1995) Electrical stimulation of the prefrontal cortex increases dopamine release in the nucleus accumbens of the rat: modulation by metabotropic glutamate receptors. J Neurosci 15:3896–3904

    Article  CAS  PubMed  Google Scholar 

  • Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT (2005) Thinning of the cerebral cortex visualized in HIV/AIDS reflect CD4(+) T lymphocyte decline. Proc Natl Acad Sci U S A 102:15647–15652. doi:10.1073/pnas.0502548102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thompson RF, Spencer WA (1966) Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73:16–43

    Article  CAS  PubMed  Google Scholar 

  • Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes O, Holck P, Grove J, Sacktor N (2004) Higher frequency of dementia in older HIV-1 individuals: the Hawaii aging with HIV-1 cohort. Neurology 63:822–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vigorito M, LaShomb AL, Chang SL (2007) Spatial learning and memory in HIV-1 transgenic rats. J NeuroImmune Pharmacol 2(4):319–328. doi:10.1007/s11481-007-9078-y

    Article  PubMed  Google Scholar 

  • Vigorito M, Connaghan KP, Chang SL (2015) The HIV-1 transgenic rat model of neuroHIV. Brain Behav Immun 48:336–349. doi:10.1016/j.bbi.2015.02.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wears RL (2002) Advanced statistics: statistical methods for analyzing cluster and cluster-randomized data. Acad Emerg Med 9:330–341

    Article  PubMed  Google Scholar 

  • Webb KM, Aksenov MY, Mactutus CF, Booze RM (2010) Evidence for developmental dopaminergic alterations in the human immunodeficiency virus-1 transgenic rat. J Neurovirol 16(2):168–173. doi:10.3109/13550281003690177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wecker JR, Ison JR, Foss JA (1985) Reflex modification as a test for sensory function. Neurobehav Toxicol Teratol 7:733–738

    CAS  PubMed  Google Scholar 

  • Wecker JR, Ison JR (1986) Visual function measured by reflex modification in rats with inherited retinal dystrophy. Behav Neurosci 100:679–684

    Article  CAS  PubMed  Google Scholar 

  • West SG, Biesanz JC, Kwok O-M (2004) Within-subject and longitudinal experiments: design and analysis issues. In: Sansone C, Morf C, Panter AT (eds) The SAGE handbook of methods in social psychology. Sage Publications, Thousand Oaks, pp 287–312

    Google Scholar 

  • Winer BJ (1971) Statistical principles in experimental design, 2nd ed. New York.

  • Wong JYF, Clifford JJ, Massalas JS, Kinsella A, Waddington JL, Drago J (2003) Essential conservation of D1 mutant phenotype at the level of individual topographies of behaviour in mice lacking both D1 and D3 dopamine receptors. Psychopharmacology 167:167–173. doi:10.1007/s00213-003-1415-0

    Article  CAS  PubMed  Google Scholar 

  • Young JS, Fechter LD (1983) Reflex inhibition procedures for animal audiometry: a technique for assessing ototoxicity. J Acoust Soc Am 73:1686–1693

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Forkstam C, Engel JA, Svensson L (2000) Role of dopamine in prepulse inhibition of acoustic startle. Psychopharmacology 149:181–188

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by grants from NIH (National Institute on Drug Abuse, DA013137; National Institute of Child Health and Human Development, HD043680; National Institute of Mental Health, MH106392; National Institute of Neurological Diseases and Stroke, NS100624) and the interdisciplinary research training program supported by the University of South Carolina Behavioral-Biomedical Interface Program. We thank Elizabeth M. Balog, Iris K. Dayton, Madison R. Gassmann, and Abigail L. Lafond for assistance with data collection.

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  1. Department of Psychology, Program in Behavioral Neuroscience, University of South Carolina, 1512 Pendleton Street, Columbia, SC, 29208, USA

    Kristen A. McLaurin, Rosemarie M. Booze & Charles F. Mactutus

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  1. Kristen A. McLaurin
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  2. Rosemarie M. Booze
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Correspondence to Charles F. Mactutus.

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The project protocol, under federal assurance (# A3049–01), was approved by the Institutional Animal Care and Use Committee (IACUC) of the University of South Carolina.

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Supplementary Figure 1

The ASR at the point of maximal inhibition is illustrated for auditory (a) and visual (b) prepulse inhibition (PPI) as a function of genotype (HIV-1 Tg, control) and age (±95% CI). (a) In auditory PPI, a linear increase in ASR at the point of maximal inhibition was observed in both HIV-1 Tg and control animals as a function of age. A global first-order polynomial was the best fit for both HIV-1 Tg and control animals; no significant differences in the rate of increase in ASR at the point of maximal inhibition was observed between genotypes [F(2,14) = 3.2, p ≥ 0.05]. (b) In visual PPI, both HIV-1 Tg and control animals displayed a linear increase in the ASR at the point of maximal inhibition as a function of age. Although the ASR at the point of maximal inhibition increased significantly faster in HIV-1 Tg animals relative to controls [F(1,14) = 14.5, p ≤ 0.002], robust inhibition to the visual prestimulus was observed at all test sessions. (GIF 57.7 kb)

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McLaurin, K.A., Booze, R.M. & Mactutus, C.F. Evolution of the HIV-1 transgenic rat: utility in assessing the progression of HIV-1-associated neurocognitive disorders. J. Neurovirol. 24, 229–245 (2018). https://doi.org/10.1007/s13365-017-0544-x

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