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Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats

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Abstract

Prepulse inhibition (PPI) of the startle reflex is reduced by systemic administration of dopamine (DA) agonists. Since PPI is impaired in patients with schizophrenia, the DA agonist-induced disruption of PPI in rats may be a useful model for studying the pathophysiology of impaired sensorimotor gating in schizophrenia. In the present study, we replicated the observation that PPI is disrupted by systemic administration of the D2 agonist quinpirole, but not by the D1 agonist SKF 38393. PPI caused by weak [1–5 dB(A)] or more intense [10 dB(A)] prepulses was also disrupted by quinpirole infusion into the nucleus accumbens (NAC). The effects of intraaccumbens quinpirole on PPI were blocked by pretreatment with the D2 antagonist haloperidol. These results support the notion that the reduction of PPI after systemic administration of DA agonists is mediated via stimulation of NAC D2 receptors.

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References

  • Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343

    Google Scholar 

  • Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215

    Google Scholar 

  • Butler RW, Braff DL, Rausch JL, Jenkins MA, Sprock J, Geyer MA (1990) Physiological evidence of exaggerated startle response in a subgroup of vietnam veterans with combat-related PTSD. Am J Psychiatry 147:1308–1312

    Google Scholar 

  • Cadenhead K, Geyer MA, Braff DL (1993) Information processing at the boundaries of schizophrenia. Biol Psychiat 33:89A

    Google Scholar 

  • Caine SB, Geyer MA, Swerdlow NR (1991) Carbachol infusion into the dentate gyrus disrupts sensorimotor gating of startle in rats. Psychopharmacology 105:347–354

    Google Scholar 

  • Costall B, Naylor RJ (1974) Extrapyramidal and mesolimbic involvement with stereotypic activity ofd- andl-amphetamine. Eur J Pharmacol 25:121–129

    Google Scholar 

  • Creese I, Iversen SD (1975) The pharmacological and anatomical substrates of the amphetamine response in the rat. Brain Res 83:419–436

    Google Scholar 

  • Davis M, Gendelman D, Tischler M, Gendelman P (1982) A primary acoustic startle circuit: lesion and stimulation studies. J Neurosci 2:791–805

    Google Scholar 

  • Davis M, Sollberger A (1971) Twenty-four hour periodicity of the startle response in rats. Psychon Sci 25:1

    Google Scholar 

  • Ison JB, McAdam DW, Hammond GR (1973) Latency and amplitude changes in the acoustic startle reflex produced by variations in auditory prestimulation. Physiol Behav 10:1035–1039

    Google Scholar 

  • Graham F (1975) The more or less startling effects of weak prestimulation. Psychophysiology 12:238–248

    Google Scholar 

  • Graham FK, Murray GM (1977) Discordant effects of weak prestimulation on magnitude and latency of the blink reflex. Physiol Psychol 5:108–114

    Google Scholar 

  • Mansbach RS, Geyer MA (1991) Parametric determinants in pre-stimulus modification of acoustic startle: interaction with ketamine. Psychopharmacology 105:162–168

    Google Scholar 

  • Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–514

    Google Scholar 

  • McGhie A, Chapman J (1961) Disorders of attention and perception in early schizophrenia. Br J Med Psychol 34:102–116

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain, 2nd edn. Plenum, New York, NY

    Google Scholar 

  • Peng RY, Mansbach RS, Braff DL, Geyer MA (1990) A D2 dopamine receptor agonist disrupts sensorimotor gating in rats: Implications for dopaminergic abnormalities in schizophrenia. Neuropsychopharmacology 3:211–218

    Google Scholar 

  • Schwartzkopf SB, Bruno JP, Mitra T (1991) Dopamine D1/D2 receptor effects on sensory gating in controls and neonatally dopamine depleted animals. Abstr Am Col Neuropsychopharmacol, p 208

  • Simmons RF (1990) Schizotypy and startle prepulse inhibition. Psychophysiology 27 [suppl.]:S6

  • Swerdlow NR, Geyer MA (1993) Prepulse inhibition of acoustic startle in rats after lesions of the pedunculopontine nucleus. Behav Neurosci 107:104–117

    Google Scholar 

  • Swerdlow NR, Geyer M, Braff D, Koob GF (1986) Central dopamine hyperactivity in rats mimics abnormal acoustic startle in schizophrenics. Biol Psychiatry 21:23–33

    Google Scholar 

  • Swerdlow NR, Mansbach RS, Geyer MA, Pulvirenti L, Koob GF, Braff DL (1990a) Amphetamine disruption of prepulse inhibition of acoustic startle is reversed by depletion of mesolimbic dopamine. Psychopharmacology 100:413–416

    Google Scholar 

  • Swerdlow NR, Braff DL, Masten VL, Geyer MA (1990b) Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens. Psychopharmacology 101:414–420

    Google Scholar 

  • Swerdlow NR, Braff DL, Geyer MA (1990c) GABAergic projection from nucleus accumbens to ventral pallidum mediates dopamine-induced sensorimotor gating deficits of acoustic startle in rats. Brain Res 532:146–150

    Google Scholar 

  • Swerdlow NR, Braff DL, Taaid N, Geyer MA (1993) Assessing the validity of an animal model of sensorimotor gating deficits in schizophrenic patients. Arch Gen Psychiat (in press)

  • Swerdlow NR, Keith VA, Braff DL, Geyer MA (1991b) The effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine-inhibition of sensorimotor gating of the startle response in the rat. J Pharmacol Exp Ther 256:530–536

    Google Scholar 

  • Swerdlow NR, Braff DL, Taaid N, Geyer MA (1992a) Assessing the validity of an animal model of sensorimotor gating deficits in schizophrenic patients. Arch Gen Psychiatry (in press)

  • Swerdlow NR, Caine SB, Braff DL, Geyer MA (1992b) Neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications. J Psychopharmacology 6:176–190

    Google Scholar 

  • Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL (1993) A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry 33:298–301

    Google Scholar 

  • Swerdlow NR, Caine SB, Geyer MA (1992d) Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. Psychopharmacology 108:189–195

    Google Scholar 

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Wan, F.J., Swerdlow, N.R. Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats. Psychopharmacology 113, 103–109 (1993). https://doi.org/10.1007/BF02244341

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  • DOI: https://doi.org/10.1007/BF02244341

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