Advertisement

Psychopharmacology

, Volume 113, Issue 3–4, pp 487–492 | Cite as

Prepulse inhibition of the acoustic startle response of rats is reduced by 6-hydroxydopamine lesions of the medial prefrontal cortex

  • Michael Bubser
  • Michael Koch
Original Investigations

Abstract

Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 × 1 µl per side) of vehicle, a low (3.0 µg/µl) or a high (6.0 µg/µl) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.

Key words

Prefrontal cortex Dopamine Acoustic startle response Prepulse inhibition 6-Hydroxydopamine Rat Schizophrenia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bean AJ, Roth RH (1991) Effects of haloperidol administration on in vivo extracellular dopamine in striatum and prefrontal cortex after partial dopamine lesions. Brain Res 549:155–158CrossRefPubMedGoogle Scholar
  2. Beckstead RM (1979) An autoradiographic examination of corticocortical and subcortical projections of the mediodorsal-projection (prefrontal) cortex in the rat. J Comp Neurol 184:43–62CrossRefPubMedGoogle Scholar
  3. Berger B, Thierry AM, Tassin JP, Moyne MA (1976) Dopaminergic innervation of the rat prefrontal cortex: a fluorescence histochemical study. Brain Res 106:133–145CrossRefPubMedGoogle Scholar
  4. Björklund A, Lindvall O (1984) Dopamine-containing systems in the CNS. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 2. Elsevier, Amsterdam, pp 55–122Google Scholar
  5. Braff DL, Stone C, Callaway E, Geyer MA, Glick ID, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343PubMedGoogle Scholar
  6. Breese GR, Traylor TD (1971) Depletion of brain noradrenaline and dopamine by 6-hydroxydopamine. Br J Pharmacol 42:88–99PubMedGoogle Scholar
  7. Bubser M (1992) Verhaltenspharmakologische und neurochemische Charakterisierung der Funktion von Dopamin im medialen präfrontalen Cortex der Ratte. PhD-thesis, Universität StuttgartGoogle Scholar
  8. Bubser M, Keseberg U, Notz PK, Schmidt WJ (1992) Differential behavioural and neurochemical effects of competitive and non-competitive NMDA receptor antagonists in rats. Eur J Pharmacol 229:75–82CrossRefPubMedGoogle Scholar
  9. Caine SB, Geyer MA, Swerdlow NR (1992) Hippocampal modulation of acoustic startle and prepulse inhibition in the rat. Pharmacol Biochem Behav 43:1201–1208Google Scholar
  10. Carter CJ, Pycock CJ (1980) Behavioural and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat. Brain Res 192:163–176CrossRefPubMedGoogle Scholar
  11. Clarke PBS, Jakubovic A, Fibiger HC (1988) Anatomical analysis of the involvement of mesolimbocortical dopamine in the locomotor stimulant actions ofd-amphetamine and apomorphine. Psychopharmacology 96:511–520Google Scholar
  12. Davis M (1988) Apomorphine,d-amphetamine, strychnine and yohimbine do not alter prepulse inhibition of the acoustic startle reflex. Psychopharmacology 95:151–156Google Scholar
  13. Deutch AY, Clark WA, Roth RH (1990) Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress. Brain Res 521:311–315CrossRefPubMedGoogle Scholar
  14. Ferron A, Thierry AM, LeDouarin C, Glowinski J (1984) Inhibitory influence of the mesocortical dopaminergic system on spontaneous activity or excitatory response induced from the thalamic mediodorsal nucleus in the rat medial prefrontal cortex. Brain Res 302:257–265CrossRefPubMedGoogle Scholar
  15. Geyer MA, 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
  16. Glowinski J, Tassin JP, Thierry AM (1984) The mesocortico-prefrontal dopaminergic neurons. TINS 7:415–418Google Scholar
  17. Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41:1–24CrossRefPubMedGoogle Scholar
  18. Hammond GR (1974) Frontal cortical lesions and prestimulus inhibition of the rat's acoustic startle reaction. Physiol Psychol 2:151–156Google Scholar
  19. Heffner TG, Hartman JA, Seiden LS (1980) A rapid method for the regional dissection of the rat brain. Pharmacol Biochem Behav 13:453–456CrossRefPubMedGoogle Scholar
  20. 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 2:175–189Google Scholar
  21. Jaskiw GE, Weinberger DR (1987) The prefrontal cortex-accumbens circuit: who's in charge? Behav Brain Sci 10:217–218Google Scholar
  22. Jaskiw GE, Weinberger DR, Crawley JN (1991) Microinjection of apomorphine into the prefrontal cortex of the rat reduces dopamine metabolite concentrations in microdialysate from the caudate nucleus. Biol Psychiatry 29:703–706CrossRefPubMedGoogle Scholar
  23. Jones GH, Robbins TW (1992) Differential effects of mesocortical, mesolimbic, and mesostriatal dopamine depletion on spontaneous, conditioned, and drug-induced locomotor activity. Pharmacol Biochem Behav 43:887–895Google Scholar
  24. Joyce EM, Stinus L, Iversen SD (1983) Effect of injection of 6-OHDA into either nucleus accumbens septi of frontal cortex on spontaneous and drug-induced activity. Neuropharmacology 22:1141–1145CrossRefPubMedGoogle Scholar
  25. Kerwin R (1992) A history of frontal and temporal lobe aspects of the neuropharmacology of schizophrenia. J Psychopharmacol 6:230–240Google Scholar
  26. Koob GF, Simon H, Herman JP, Le Moal M (1984) Neuroleptic-like disruption of the conditioned avoidence response requires destruction of both the mesolimbic and nigrostriatal dopamine systems. Brain Res 303:319–329CrossRefPubMedGoogle Scholar
  27. Le Moal M, Simon H (1991) Mesocorticolimbic dopaminergic network: functional and regulatory roles. Physiol Rev 71:155–234PubMedGoogle Scholar
  28. Leonard CM (1969) The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections. Brain Res 12:321–343CrossRefPubMedGoogle Scholar
  29. Louilot A, Le Moal M, Simon H (1989) Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study. Neuroscience 29:45–56CrossRefPubMedGoogle Scholar
  30. Oades RD, Taghzouti K, Rivet JM, Simon H, Le Moal M (1986) Locomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal and frontal areas: a 6-hydroxydopamine study. Neuropsychobiology 16:37–42PubMedGoogle Scholar
  31. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, New YorkGoogle Scholar
  32. Peterson SL, St Mary JS, Harding NR (1987) Cis-flupentixol antagonism of the rat prefrontal cortex neuronal response to apomorphine and ventral tegmental area input. Brain Res Bull 18:723–729CrossRefPubMedGoogle Scholar
  33. Pilz PKD, Schnitzler HU, Menne D (1987) Acoustic startle threshold of the albino rat (Rattus norvegicus). J Comp Psychol 101:67–72CrossRefPubMedGoogle Scholar
  34. Pycock CJ, Kerwin RW, Carter CJ (1980) Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats. Nature 286:74–77CrossRefPubMedGoogle Scholar
  35. Robbins TW (1990) The case for frontostriatal dysfunction in schizophrenia. Schizophr Bull 16:391–402PubMedGoogle Scholar
  36. Romo R, Chéramy A, Godeheu G, Glowinski J (1986) In vivo presynaptic control of dopamine release in the cat caudate nucleus — III further evidence for the implication of corticostriatal glutamatergic neurons. Neuroscience 19:1091–1099CrossRefPubMedGoogle Scholar
  37. Sesack SR, Bunney BS (1989) Pharmacological characterization of the receptors mediating electrophysiological responses to dopamine in the rat medial prefrontal cortex: a microiontophoretic study. J Pharmacol Exp Ther 248:1323–1333PubMedGoogle Scholar
  38. Sesack SR, Pickel VM (1992) Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area. J Comp Neurol 320:145–160CrossRefPubMedGoogle Scholar
  39. Sesack SR, Deutch AY, Roth RH, Bunney BS (1989) Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin. J Comp Neurol 290:213–242CrossRefPubMedGoogle Scholar
  40. Swerdlow NR, Braff DL, Geyer MA, Koob GF (1986) Central dopamine hyperactivity in rats mimics abnormal acoustic startle response in schizophrenics. Biol Psychiatry 21:23–33CrossRefPubMedGoogle Scholar
  41. Swerdlow NJ, Braff DL, Masten VL, Geyer MA (1990) Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens. Psychopharmacology 101:414–420Google Scholar
  42. Swerdlow NR, Caine SB, Braff DL, Geyer MA (1992a) The neural substrates of sensorimotor rating of the startle reflex: a review of recent findings and their implications. J Psychopharmacol 6:176–190Google Scholar
  43. Swerdlow NR, Caine SB, Geyer MA (1992b) Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. Psychopharmacology 108:189–195Google Scholar
  44. Taghzouti K, Simon H, Hervé D, Blanc G, Studler JM, Glowinski J, LeMoal M, Tassin JP (1988) Behavioural deficits induced by the electrolytic lesion of the rat ventral mesencephalic tegmentum are corrected by a superimposed lesion of the dorsal nordrenergic system. Brain Res 440:172–176CrossRefPubMedGoogle Scholar
  45. Tassin JP (1987) Dopamine and mental illness: and what about the mesocortical dopamine systems? Behav Brain Sci 10:224–225Google Scholar
  46. Vezina P, Blanc G, Glowinski J, Tassin JP (1991) Opposed behavioural outputs of increased dopamine transmission in prefrontocortical and subcortical areas: a role for the cortical D-1 dopamine receptor. Eur J Neurosci 3:1001–1007PubMedGoogle Scholar
  47. Youngren KD, Daly DA, Moghaddam B (1993) Distinct actions of endogenous excitatory amino acids on the outflow of dopamine in the nucleus accumbens. J Pharmacol Exp Ther 264:289–293PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Michael Bubser
    • 1
  • Michael Koch
    • 2
  1. 1.Abteilung NeuropharmakologieUniversität TübingenTübingenGermany
  2. 2.Tierphysiologie, Universität TübingenTübingenGermany

Personalised recommendations