, Volume 108, Issue 1–2, pp 189–195 | Cite as

Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats

  • N. R. Swerdlow
  • S. B. Caine
  • M. A. Geyer
Original Investigations


Systemic administration of dopamine (DA) agonists markedly disrupts sensorimotor gating in rats as measured by prepulse inhibition (PPI) of the acoustic startle response. A qualitatively similar, but quantitatively weaker disruption of PPI follows DA infusion into the nucleus accumbens (NAC). The present study was designed to determine whether forebrain DA terminal fields other than the NAC contribute to the DAergic modulation of PPI. PPI was impaired significantly after infusion of DA (0–40 µg) into the NAC or anteromedial striatum, but not after DA infusion into the orbital cortex or posterolateral striatum. DA infusion into the amygdala also disrupted PPI, but this disruption was accompanied by a dose-dependent decrease in startle amplitude. These results suggest that DA overactivity in the both NAC and anteromedial striatum contribute to the gating-disruptive effects of systemically administered DA agonists, and that DA overactivity in mesocortical, mesoamygdaloid and “non-limbic” mesostriatal DA systems are not major substrates for a DAergic modulation of PPI.

Key words

Acoustic startle response Amygdala Dopamine Nucleus accumbens Orbital cortex Prepulse inhibition Sensorimotor gating Striatum 


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  1. Bickford-Wimer PC, Nagamoto H, Johnson R, Adler LE, Egan M, Rose GM, Freedman R (1990) Auditory sensory gating in hippocampal neurons: a model system in the rat. Biol Psychiatry 27:183–192CrossRefPubMedGoogle Scholar
  2. Braff DL, Geyer MA (1990) Sensorimotor gating and schizophrenia: human and animal model studies. Arch Gen Psychiatry 47:181–188PubMedGoogle Scholar
  3. Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343PubMedGoogle Scholar
  4. Braff DL, Grillon C, Geyer MA (1992) Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 49:206–215PubMedGoogle Scholar
  5. Caine SB, Geyer MA, Swerdlow NS (1991) Carbachol infusion into the dentate gyrus disrupts sensorimotor gating of the startle reflex in rats. Psychopharmacology 105:347–354CrossRefPubMedGoogle Scholar
  6. Davis M (1980) Neurochemical modulation of sensory-motor reactivity: acoustic and tactile startle reflexes. Neurosci Biobehav Rev 4:241–263CrossRefPubMedGoogle Scholar
  7. Davis M, Aghajanian GK (1976) Effects of apomorphine and haloperidol on the acoustic startle response in rats. Psychopharmacology 47:217–223CrossRefPubMedGoogle Scholar
  8. Davis M, Gendelman D, Tischler M, Gendelman P (1982) A primary acoustic startle circuit: lesion and stimulation studies. J Neurosci 2:791–805PubMedGoogle Scholar
  9. Davis M, Mansbach RS, Swerdlow NR, Braff DL, Geyer MA (1990) Apomorphine disrupts the inhibition of acoustic startle induced by weak prepulses in rats. Psychopharmacology 102:1–4Google Scholar
  10. Early TS, Relman EM, Raichle ME, Spitzmagel EL (1987) Left globus pallidus abnormality in newly medicated patients with schizophrenia. Proc Natl Acad Sci USA 84:561–563PubMedGoogle Scholar
  11. Geyer M, Swerdlow NR, Mansbach RS, Braff DL (1990) Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res Bull 25:485–498CrossRefPubMedGoogle Scholar
  12. Graham F (1975) The more or less startling effects of weak prestimulation. Psychophysiology 12:238–248PubMedGoogle Scholar
  13. Grillon C, Ameli R, Braff DL (1991) Sensorimotor gating deficits in schizophrenia: Replication and extension using the startle response. Biol Psychiatry 29:164AGoogle Scholar
  14. Heimer L, Wilson RD (1975) The subcortical projections of the allocortex: Similarities in the neural associations of the hippocampus, the piriform cortex and the neocortex. In: Santini M (ed) Golgi Centennial Symposium Proceedings. Raven Press, New York, pp 177–193Google Scholar
  15. Hoffman HS, Searle JL (1968) Acoustic and temporal factors in the evocation of startle. J Acoust Soc Am 43:269–282CrossRefPubMedGoogle Scholar
  16. Leitner DS, Powers AS, Stitt AS, Hoffman HS (1981) Midbrain reticular formation involvement in the inhibition of acoustic startle. Physiol Behav 26:259–269CrossRefPubMedGoogle Scholar
  17. Luchins DJ (1990) A possible role of hippocampal dysfunction in schizophrenic symptomatology. Biol Psychiatry 28:87–91CrossRefPubMedGoogle Scholar
  18. Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–514PubMedGoogle Scholar
  19. Mogenson GJ, Nielsen M (1984) A study of the contribution of hippocampal-accumbens-subpallidal projections to locomotor activity. Behav Neural Biol 42:52–60CrossRefPubMedGoogle Scholar
  20. Nauta WJH, Smith GP, Domesick VB, Faull RLM (1978) Efferent connections and nigral afferents of the nucleus accumbens septi in the rat. Neuroscience 3:385–401CrossRefPubMedGoogle Scholar
  21. Pakkenberg B (1990) Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 47:1023–1028PubMedGoogle Scholar
  22. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, AustraliaGoogle Scholar
  23. Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain. Plenum Press, New YorkGoogle Scholar
  24. 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 3:211–218PubMedGoogle Scholar
  25. Penney JB, Young AB (1983) Speculations on the functional anatomy of basal ganglia disorders. Annu Rev Neurosci 6:73–94CrossRefPubMedGoogle Scholar
  26. Saitoh K, Tilson HA, Shaw S, Dyer RS (1987) Possible role of the brainstem in the mediation of prepulse inhibition in the rat. Neurosci Lett 75:216–222CrossRefPubMedGoogle Scholar
  27. Swanson LW, Mogenson GJ, Gerfen CR, Robinson P (1984) Evidence for a projection from the lateral preoptic area and substantia innominata to the ‘mesencephalic locomotor region’ in the rat. Brain Res 295:161–178CrossRefPubMedGoogle Scholar
  28. Swerdlow NR, Geyer M, Braff D, Koob GF (1986) Central dopamine hyperactivity in rats mimics abnormal acoustic startle in schizophrenics. Biol Psychiatry 21:23–33CrossRefPubMedGoogle Scholar
  29. 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 100:413–416CrossRefPubMedGoogle Scholar
  30. Swerdlow NR, Braff DL, Masten VL, Geyer MA (1990b) Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens Psychopharmacology 101:414–420CrossRefPubMedGoogle Scholar
  31. Swerdlow NR, Keith VA, Braff DL, Geyer MA (1991a) 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 256:530–536PubMedGoogle Scholar
  32. Swerdlow NR, Caine B, Geyer MA (1992b) Sensorimotor gating of the startle reflex is mediated by ventral pallidal efferents to the pedunculopontine nucleus. Abstr Soc Neurosci (in press)Google Scholar
  33. 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 532:146–150CrossRefPubMedGoogle Scholar
  34. Wong D, Wagner H, Tune L, Dannals R, Pearlson G, Links J, Tamminga C, Broussolle E, Ravert H, Wilson A, Toung J, Malat J, Williams J, O'Tuama L, Snyder S, Kuhar M, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558–1563PubMedGoogle Scholar
  35. Young KA, Randall PK, Wilcox RE (1990) Effect of thalamic microinjection of apomorphine and muscimol on the acoustic startle response and other behaviors. Abstr Soc Neurosci 16:426Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • N. R. Swerdlow
    • 1
  • S. B. Caine
    • 1
  • M. A. Geyer
    • 1
  1. 1.0804, Department of Psychiatry, School of MedicineUniversity of CaliforniaSan Diego, La JollaUSA

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