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Specific effects of the benzodiazepine midazolam on visual receptive fields in light and dark adapted human subjects

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Abstract

Psychophysical experiments in humans have revealed similar characteristics of visual receptive fields as were found in cats and monkeys from retinal ganglion cell recordings. In addition, in some retinal ganglion cells of cats the GABA antagonist bicuculline decreases the activity of the inhibitory surround. These findings led to two predicitions: 1) benzodiazepines will selectively increase the inhibitory surround of human visual receptive fields, 2) after dark adaptation, no free GABA will be available in the synapses and benzodiazepines will have no effect on the visual system. Characteristics of human receptive fields were determined by subthreshold summation: the contrast threshold of a vertical line was measured dependent on the distance of two parallel flanking lines whose contrast was below threshold. Both hypotheses were confirmed: the threshold in the inhibitory region of receptive fields was specifically increased in a dose-dependent manner by midazolam PO (7.5 mg:P<0.05; 15 mg:P<0.01). In dark-adapted subjects no effect of midazolam was found. Control experiments with atropine (1 mg IV), sulpiride (100 mg IM), and levodopa (100 mg PO) showed no specific effect. The visual system may be a model to bridge the gap between animal and human psychopharmacology.

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References

  • Baktir G, Fisch HU, Huguenin P, Bircher J (1983) Triazolam concentration-effect relationship in healthy volunteers. Clin Pharmacol Ther 34:195–201

    PubMed  Google Scholar 

  • Baktir G, Fisch HU, Karlaganis G, Minder C, Bircher H (1987) Mechanisms of the excessive sedative response of cirrhotics to benzodiazepines: model experiments with triazolam. Hepatology 7:629–638

    PubMed  Google Scholar 

  • Barlow HB (1983) Understanding natural vision. In: Braddick OJ, Sleigh AC (eds) Physical and biological processing of images. Springer, Berlin Heidelberg New York, pp 4–13

    Google Scholar 

  • Barlow HB, Fitzhugh R, Kuffer SW (1957) Change of organization in the receptive fields of the cat's retina during dark adaptation. J Physiol 137:338–354

    PubMed  Google Scholar 

  • Barlow HB, Derington AM, Harris LR, Lennie P (1977) The effects of remote retinal stimulation on the responses of cat retinal ganglion cells. J Physiol 269:177–194

    PubMed  Google Scholar 

  • Biggio G, Guarneri P, Corda MG (1981) Benzodiazepine and GABA receptors in the rat retina: effect of light and dark adaptation. Brain Res 216:210–214

    Article  PubMed  Google Scholar 

  • Bloom F (1987) Future directions and goals in basic psychopharmacology and neurobiology. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 1685–1689

    Google Scholar 

  • Bowling A (1985) The effects of peripheral movement and flicker on the detection thresholds of sinusoidal gratings. Percep Psychophys 37:181–188

    Google Scholar 

  • Branch R (1987) Is there increased cerebral sensitivity to benzodiazepines in chronic liver disease? (Editorial). Hepatology 7:773–776

    PubMed  Google Scholar 

  • Brecha N, Johnson D, Peichl L, Waessle H (1988) Cholinergic amacrine cells of the rabbit retina contain glutamate decarboxylase and gamma-amino butyrate immunoreactivity. Neurobiology 85:6187–6191

    Google Scholar 

  • Breitmeyer BG, Valberg A, Kurtenbach W, Neumeyer C (1980) The lateral effect of oscillation of peripheral luminance gratings on the foveal increment threshold. Vision Res 20:799–805

    Article  PubMed  Google Scholar 

  • Caelli T (1981) Visual perception, theory and practice. Pergamon Press, Oxford Caldwell-JH, Daw NW (1978) Effects of picrotoxine and strychnine on rabbit retinal ganglion cells: changes in centre surround receptive fields. J Physiol 276:299–310

    Google Scholar 

  • Chentanez T, Redburn Dianna A (1987) Synaptosomal neurotransmitter uptake systems in the retina and brain nuclei of light- and dark-adapted rabbits. Brain Res 424:115–118

    Article  PubMed  Google Scholar 

  • Creese I (1987) Biochemical properties of CNS dopamine receptors. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 257–264

    Google Scholar 

  • Cunningham JR, Dawson C, Neal MJ (1983) Evidence for a cholinergic inhibitory feed-back mechanism in the rabbit retina. J Physiol 340:455–468

    PubMed  Google Scholar 

  • Daw NW, Ariel M (1981) Effect of synaptic transmitter drugs on receptive fields of rabbit retinal ganglion cells. Vision Res 21:1643–1647

    Article  PubMed  Google Scholar 

  • Dixon AK, McAllister KH, Fisch HU (1990) Ethopharmacology. Adv Stud Behav 19:171–190

    Google Scholar 

  • Domenici L, Trimarchi C, Piccolino M, Fiorentini A, Maffei L (1985) Dopaminergic drugs improve human visual contrast sensitivity. Hum Neurobiol 4:195–197

    PubMed  Google Scholar 

  • Düker HC (1964) Die reaktive Anpassungssteigerung als Störfaktor bei der Wirkungsprüfung von Schlafmitteln. In: Bradley PB, Flügel F, Hoch PH (eds) Proceedings of the third meeting of the collegium internationale neuro-psychopharmacologicum. Elsevier, Amsterdam, pp 172–175

    Google Scholar 

  • Dundee JW, Halliday NJ, Harper KW, Brogden RN (1984) Midazolam. A review of its pharmacological properties and therapeutic use. Drugs 28:519–543

    PubMed  Google Scholar 

  • Emre M, Groner M, Hofer D, Walder F, Fisch HU (1989) The effects of the benzodiazepine midazolam on a visual perceptive function, backward and forward masking. Clin Vis Sci 23:257–263

    Google Scholar 

  • Enna SJ, Möhler H (1987) Gamma-aminobutyric acid (GABA) receptors and their association with benzodiazepine recognition sites. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 265–272

    Google Scholar 

  • Enroth-Cugell C, Robson JG (1966) The contrast sensitivity of retinal ganglion cells of the cat. J Physiol 187:517–552

    Google Scholar 

  • Fiorentini A, Mazzantini L (1966) Neural inhibition in the human fovea: a study of interactions between two line stimuli. Atti Fond Giorgio Ronchi 21:738–747

    Google Scholar 

  • Fisch HU, Groner M, Groner R, Menz C (1983) Influence of diazepam and methylphenidate on identification of rapidly presented letter strings: diazepam enhances visual masking. Psychopharmacology 80:61–66

    Article  PubMed  Google Scholar 

  • Fischer B, Krüger J (1974) The shift-effect in the cat's lateral geniculate neurons. Exp Brain Res 21:225–227

    Article  PubMed  Google Scholar 

  • Fischer B, Barth R, Sternheim CE (1978) Interaction of receptive field responses and shift-effect in cat retinal and geniculate neurons. Exp Brain Res 31:235–248

    Article  PubMed  Google Scholar 

  • Gallager DW, Tallman JF (1990) Relationship of GABA-A receptor heterogeneity to regional differences in drug response. Neurochem Res 15:113–118

    Article  PubMed  Google Scholar 

  • Haefely W, Martin JR, Schoch P (1990) Novel anxiolytics that act as partial agonists at benzodiazepine receptors. TIPS 11:452–456

    PubMed  Google Scholar 

  • Harris JP, Calvert JE, Leendertz JA, Phillipson OT (1990) The influence of dopamine on spatial vision. Eye 4:806–812

    PubMed  Google Scholar 

  • Hindmarch I (1981) Psychomotor function and psychoactive drugs. In: Lader MH, Richens A (eds) Methods in clinical pharmacology—central nervous system. Macmillan, London, pp 29–50

    Google Scholar 

  • Hines M (1976) Line spread function variation near the fovea. Vision Res 16:567–572

    Article  PubMed  Google Scholar 

  • Jensen RJ, Daw NW (1986) Effects of dopamine and its agonists and antagonists on the receptive field properties of ganglion cells in the rabbit retina. Neuroscience 17(3):837–855

    Article  PubMed  Google Scholar 

  • Jung R (1978) Einführung in die Sehphysiologie. In: Baumgartner G, Bornschein H, Hanitzsch R, Jung R, Kornhuber HH, Rentschler et al. (eds) Sehen. Sinnesphysiologie III. Urban & Schwarzenberg, München, pp 1–140

    Google Scholar 

  • King-Smith PE, Kulikowski JJ (1975) Pattern and flicker detection analysed by subthreshold summation. J Physiol 249:519–548

    PubMed  Google Scholar 

  • Kirby AW (1979) The effect of strychnine, bicuculline, and picrotoxin on X and Y cells in the cat retina. J Gen Physiol 74:71–84

    Article  PubMed  Google Scholar 

  • Kirby AW, Enroth-Cugell C (1976) The involvement of gamma-aminobutyric acid in the organization of cat retinal ganglion cell receptive fields. J Gen Physiol 68:465–484

    Article  PubMed  Google Scholar 

  • Kirby AW, Schweitzer-Tong DE (1981) GABA-antagonists and spatial summation in y-type cat retinal ganglion cells. J Physiol 312:335–344

    PubMed  Google Scholar 

  • Krüger J, Fischer B (1973) Strong periphery effect in cat retinal ganglion cells. Excitatory responses in ON- and OFF-center neurons to single grid displacements. Exp Brain Res 18:316–318

    PubMed  Google Scholar 

  • Krüger J, Fischer B, Barth R (1975) The shift-effect in retinal ganglion cells of the rhesus monkey. Exp Brain Res 23:443–446

    Article  PubMed  Google Scholar 

  • Kuffler SW, Nicholls JG (1976) From neuron to brain. Sinauer Associates, Sunderland, Massachusetts

    Google Scholar 

  • Kulikowski JJ, King-Smith PE (1973) Spatial arrangement of line, edge and grating detectors revealed by subthreshold summation. Vision Res 13:1455–1478

    Article  PubMed  Google Scholar 

  • MacKay DM (1987) Psychophysics and neurophysiology. In: George Adelman (ed) Encyclopedia of neuroscience. Birkhäuser, pp 1008–1010

  • Malcolm SL, Allen JJ, Bird H, Quinn NP, Marion MH, Marsden CD et al. (1987) Single dose pharmacokinetics of madopar HBS in patients and effect of food and antacid on the absorption of madopar HBS in volunteers. Eur Neurol 27 [suppl 1]:28–35

    PubMed  Google Scholar 

  • Masland RH, Ames A (1982) Responses to acetylcholine of ganglion cells in an isolated mammalian retina. J Neurophysiol 1976; 39:1220–1235

    Google Scholar 

  • Massey SC, Redburn DA (1982) A tonic gamma-aminobutyric acid-mediated inhibition of cholinergic amacrine cells in rabbit retina. J Neurosci 2:1633–1643

    PubMed  Google Scholar 

  • Mattingley JB, Badcock DR (1991) The shift effect can be elicited with both foveal and peripheral masks. Vision Res 31 [7/8]:1251–1257

    Article  PubMed  Google Scholar 

  • Mcllwain JT (1964) Receptive fields of optic tract axons and lateral geniculate cells: peripheral extent and barbiturate sensitivity. J Neurophysiol 27:1154–1173

    PubMed  Google Scholar 

  • Mcllwain JT (1966) Some evidence concerning the physiological basis of the periphery effect in the cat's retina. Exp Brain Res 1:265–271

    PubMed  Google Scholar 

  • Morgan WW, Kamp CW (1980) A GABA-ergic influence on the light-induced increase in dopamine turnover in the dark-adapted rat retina in vivo. J Neurochem 34:1082–1086

    PubMed  Google Scholar 

  • Pentland A (1980) Maximum likelihood estimation: the best PEST. Percep Psychophys 28[4]:377–379

    Google Scholar 

  • Ransom-Hogg A, Spillmann L (1980) Perceptive field size in fovea and periphery of the light- and dark-adapted retina. Vision Res 20:221–228

    Article  PubMed  Google Scholar 

  • Robbins J, Ikeda H (1989) Benzodiazepines and the mammalian retina. II. Actions on retinal ganglion cells. Brain Res 479:323–333

    Article  PubMed  Google Scholar 

  • Saito HA (1981) The effects of strychnine and bicuculline on the responses of X-and Y-cells of the isolated eye-cup preparation of the cat. Brain Res 212:243–248

    Article  PubMed  Google Scholar 

  • Saito HA (1983) Pharmacological and morphological differences between X- and Y-type ganglion cells in cats retina. Vision Res 23:1299–1308

    Article  PubMed  Google Scholar 

  • Schlaepfer T, Groner M, Lavoyer E, Fisch HU (1991) Visual Masking: a reliable measure for the assessment of cognitive dysfunction in the elderly? J Geronto Psychol Sci 46[4]:157–161

    Google Scholar 

  • Snyder SH (1987) Molecular strategies in neuropsychopharmacology: old and new. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 17–21

    Google Scholar 

  • Spillmann L, Levine J (1971) Contrast in a Hermann grid with variable figure-ground ratio. Exp Brain Res 13:547–559

    Article  PubMed  Google Scholar 

  • Spillmann L, Ransom-Hogg A, Oehler R (1987) A comparison of perceptive and receptive fields in man and monkey. Hum Neurobiol 6:51–62

    PubMed  Google Scholar 

  • Teller DY (1980) Locus questions in visual science. In: Harris CS (ed) Visual coding and adaptability. Lawrence Erlbaum, Hillsdale, New Jersey, pp 151–176

    Google Scholar 

  • Weiner N (1985) Atropine, scopolamine, and related antimuscarinic drugs. In: Goodman and Gilman's. The pharmacological basis of therapeutics. Macmillan, New York, pp 130–144

    Google Scholar 

  • Westheimer G (1965) Spatial interaction in the human retina during scotopic vision. J Physiol 181:881–994

    PubMed  Google Scholar 

  • Westheimer G (1967) Spatial interaction in human cone vision. J Physiol 190:139–154

    PubMed  Google Scholar 

  • Wilson HR (1978) Quantitative characterization of two types of line-spread function near the fovea. Vision Res 18:971–981

    Article  PubMed  Google Scholar 

  • Wilson HR, Bergen JR (1979) A four mechanism model for threshold spatial vision. Vision Res 19:19–32

    Article  PubMed  Google Scholar 

  • Yazulla S (1983) GABAergic mechanisms in the retina. In: Progress in retinal research, vol 3. Pergamon Press, Oxford, pp 1–52

    Google Scholar 

  • Yeh HH, Battelle BA, Puro DG (1984) Dopamine regulates synaptic transmission mediated by cholinergic neurons of the rat retina. Neuroscience 13[3]:901–909

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychology, University of Berne, CH-3010, Berne, Switzerland

    M. Groner, F. Walder, R. Groner & D. Hofer

  2. Department of Psychiatry, University of Berne, CH-3010, Berne, Switzerland

    H. -U. Fisch, U. Koelbing, I. Duss, R. Bianchi & B. Bircher

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  1. M. Groner
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  2. H. -U. Fisch
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  3. F. Walder
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  4. R. Groner
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  5. D. Hofer
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  6. U. Koelbing
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  7. I. Duss
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  8. R. Bianchi
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  9. B. Bircher
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Groner, M., Fisch, H.U., Walder, F. et al. Specific effects of the benzodiazepine midazolam on visual receptive fields in light and dark adapted human subjects. Psychopharmacology 109, 68–76 (1992). https://doi.org/10.1007/BF02245482

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  • DOI: https://doi.org/10.1007/BF02245482

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