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Nicotinic cholinergic normalization of amphetamine-induced loss of auditory gating in freely moving rats

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The impairment in normal sensory processing which is usually observed in schizophrenics has been demonstrated using a paired-stimulus paradigm. Normal individuals show a diminished midlatency evoked potential response to the second of a pair of clicks given at a 0.5-s interval. This phenomenon is termed auditory “gating”. Schizophrenics routinely fail to suppress their response to the second click in this paradigm; thus, they do not gate. Heavy tobacco use is common among schizophrenics and it has recently been shown that nicotine causes a transient normalization of auditory gating in these individuals. Our laboratory has been utilizing animal models to investigate the sensory deficit observed in schizophrenia. In the present study, rats were administered amphetamine to produce a schizophrenia-like loss of auditory gating. They were then given nicotine, which resulted in a dose-dependent normalization of the amphetamine-induced loss of gating. This effect was blocked by concurrent central administration ofd-tubocurarine. Neither nicotine nord-tubocurarine had any effect on auditory gating when administered alone. These data are in agreement with the human studies showing normalization of auditory gating with nicotine administration and suggest a possible role for the nicotinic cholinergic receptor in the modulation of auditory gating in the rat model.

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  1. Acri JB, Morse DE, Popke EJ, Grunberg NE (1994) Nicotine increases sensory gating measured as inhibition of the acoustic startle reflex in rats. Psychopharmacology 114:369–374

  2. Adler LE, Rose G, Freedman R (1986) Neurophysiological studies of sensory gating in rats: effects of amphetamine, phencyclidine and haloperidol. Biol Psychiat 21:787–798

  3. Adler LE, Hoffer LH, Wiser A, Freedman R (1993) Transient normalization of a defect in auditory sensory processing in schizophrenics following cigarette smoking. Am J Psychiatry 150:1856–1860

  4. Adler LE, Gerhardt GA, Franks R, Baker N, Nagamoto H, Drebing C, Freedmam R (1990) Sensory physiology and catecholamines in schizophrenia and mania. Psychiatry Res 31:297–309

  5. Adler LE, Hoffer LH, Griffith J, Waldo M, Freedman R (1992) Normalization of deficient auditory sensory gating in the relatives of schizophrenics by nicotine Biol Psychiat 32:607–616

  6. Adler LE, Pang K, Gerhardt G, Rose GM (1988) Modulation of the gating of auditory evoked potentials by norepinephrine: pharmacological evidence obtained using a selective neurotoxin. Biol Psychiatry 24:179–190

  7. Amos A, Armstrong DM, Marple-Horvat DE (1990) Changes in the discharge patterns of motor cortical neurones associated with volitional changes in stepping in the cat. Neurosci Lett 109:107–112

  8. Baker N, Adler LE, Franks RD, Waldo M, Berry S, Nagamoto H, Muckle A, Freedman R (1987) Neurophysiological assessment of gating of sensory input: Comparison between schizophrenia and other diagnoses. Biol Psychiatry 22:603–617

  9. Braff DL, Geyer M (1990) Sensorimotor gating and schizophrenia. Arch Gen Psychiatry 47:181–188

  10. Broadbent DE (1985) Perception and communication. Pergamon Press, London

  11. Curzon P, Kim DJB, Decker MW (1993) Effect of nicotine and mecamylamine on sensorimotor gating in the rat. Soc Neurosci Abs 19:201

  12. Dashieff RM (1985)d-Tubocurarine causes neuronal death when injected directly into rat brain. Exp Neurol 89:172–188

  13. Egan TM, North RA (1986) Actions of acetylcholine and nicotine on rat locus coeruleus neurons in vitro. Neuroscience 19:565–571

  14. Freedman R, Adler LE, Waldo MC, Pachtman E, Franks RD (1983) Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: Comparison of medicated and drug-free patients. Biol Psychiatry 18:537–551

  15. Freedman R, Adler LE, Baker N, Rose G, Waldo M, Franks R, Pang K, Drebing C, Gerhardt G, Bickford P (1986) Noradrenergic and dopaminergic modulation of auditory evoked potential in schizophrenia and mania. Am Col Neuropsychopharmacol Abstr 25:147

  16. Freedman R, Adler LE, Gerhardt GA, Waldo M, Baker N, Rose GM, Drebing C, Nagamoto H, Bickford-Wimer P, Franks R (1987) Neurobiological studies of sensory gating in schizophrenia. Schizophr Bull 13:669–678

  17. Goff DC, Henderson DC, Amico E (1992) Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatry 149:1189–1194

  18. Greenman M, McClellan TA (1991) Negative effects of a smoking ban on an impatient psychiatry service. Hosp Commun Psychiat 42:408–412

  19. Harris KR, Stevens KE, Lehman JC, Rose GM (1993) Spontaneously non-gating rats: A model of the auditory gating deficit in schizophrenia. Soc Neurosci Abstr 19:837

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

  21. Holzman PS, Kringlen E, Matthysse S, Flanagan SD, Lipton D, Cramer RB, Levin G, Lange S, Levey DL (1988) A single dominant gene can account for eye tracking dysfunctions and schizophrenia in offspring of discordant twins. Arch Gen Psychiat 45:641–647

  22. Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA (1986) Prevalence of smoking among psychiatric outpatients. Am Psychiatry 143:993–997

  23. Ison JR, Hoffman, HS (1983) Reflex modifications in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon. Psychol Bull 94:3–17

  24. Kathman N, Engel RR (1990) Sensory gating in normals and schizophrenics: a failure to find strong P50 suppression in normals. Biol Psychiatry 27:1216–1226

  25. Klein C, Andersen B (1991) On the influence of smoking upon smooth pursuit eye movements of schizophrenics and normal controls. J Psychophysiol 5:361–369

  26. Koelle GB (1972) Acetylcholine-current status in physiology, pharmacology and medicine. N Eng J Med 286:1086–1090

  27. Kuhar MJ, Ritz MC, Boja JW (1991) The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci 14:299–302

  28. Lunts-Leybman V, Bickford PC, Freedman R (1992) Cholinergic gating of response to auditory stimuli in rat hippocampus. Brain Res 587:130–136

  29. Malone HM, Peters JA, Lambert JJ (1991) Physiological and pharmacological properties of 5-HT3 receptors — A patch clamp-study. Neuropeptides 19 [suppl]:25–30

  30. Marks MJ, Stitzel JA, Romm E, Wehner JM, Collins AC (1986) Nicotinic binding sites in rat and mouse brain: Comparison of acetylcholine, nicotine andα-bungarotoxin. Mol Pharmacol 30:427–436

  31. Masterson E, O'Shea B (1984) Smoking and malignancy in schizophrenia. Br J Psychiatry 145:429–432

  32. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, San Oiego

  33. Reulecke M, Hucho F (1985) High- and low-affinity binding of [3H]acetylcholine at nicotinic cholinergic receptors in rat brain. Neurosci Lett 59:271–276

  34. Stevens KE, Fuller LL, Rose GM (1991) Dopaminergic and noradrenergic modulation of amphetamine-induced changes in auditory gating potentials. Brain Res 555:91–98

  35. Stevens KE, Freedman R, Hall M, Leonard S, Rose GM (1993a) Hippocampal CA3 α-bungarotoxin binding is correlated with auditory gating ability in inbred mouse strains. Soc Neurosci Abstr 19:465

  36. Stevens KE, Freedman R, Rose GM (1993b) Mouse strains with differing numbers of hippocampal α-bungarotoxin binding sites display varying ability to gate to paired auditory stimuli. Schizopr Res 9:168

  37. Stolerman IP, Fink R, Jarvik ME (1973) Acute and chronic tolerance to nicotine measured by activity in rats. Psychopharmacology 30:329–342

  38. Venables PH (1992) Hippocampal function and schizophrenia. Experimental psychological evidence. Ann NY Acad Sci 658:111–127

  39. Venables P (1964) Input dysfunction in schizophrenia. In: Maher BA (ed) Progress in experimental personality research. Academic Press, Orlando, pp 1–47

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Correspondence to Gregory M. Rose.

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Stevens, K.E., Meltzer, J. & Rose, G.M. Nicotinic cholinergic normalization of amphetamine-induced loss of auditory gating in freely moving rats. Psychopharmacology 119, 163–170 (1995).

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Key words

  • Auditory evoked potentials
  • Schizophrenia
  • d-Tubocurarine
  • Sensory gating