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Effects of ethanol and imidazobenzodiazepine Ro 15-4513 on spontaneous saccades of the pigmented rat

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The present study was aimed at investigating the alterations of the spontaneous saccadic eye movements of pigmented rats following ethanol administration. In addition we have studied the efficacy of the imidazobenzodiazepine Ro 15-4513 in reversing the effects of alcohol on saccades. The horizontal component of spontaneous eye movements was recorded by means of the magnetic field search coil technique on 11 head-restrained, pigmented rats. After the intraperitoneal injection of ethanol (1 g/kg) spontaneous saccades showed: i) a backward post-saccadic drift, with an exponentiallike time course (time constant 100–150 ms); ii) a remarkable reduction of mean saccadic amplitude, up to 37% of control; iii) a significant decrease of peak velocity, which was reduced to about 80% of control. All these effects appeared and developed within a few minutes after the administration and were still present one hour later. When Ro 15-4513 (5 mg/kg) was injected i.p., 15 min after ethanol, the post-saccadic drift amplitude was immediately reduced and the drift was completely abolished within about 30 min. Mean saccadic amplitude returned to control values within a few minutes and was then steadily maintained for the following period examined (30 min). On the contrary, peak velocity showed only a slight tendency to recover which never was significant. When the same dose of Ro 15-4513 was injected alone there was no post-saccadic drift. However, mean saccadic amplitude increased, almost immediately, up to 160% of control. Its value showed a slight constant decrease in the following 30 min. Peak velocity was only slightly increased (up to 106% of control), but never was significantly different from control. Our results show that ethanol induces a remarkable impairment in the performance of spontaneous saccades. The imidazobenzodiazepine Ro 15-4513 is able to reverse completely only some of the alcohol-induced alterations, i.e. the posts-accadic drift and the reduction of saccadic amplitude, while it fails to counter efficiently the reduction of peak velocity. Ro 15-4513 exerts an intrinsic action, which is opposite to that of ethanol, on some of the saccadic parameters we have examined.

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References

  • Andersson SI (1984) Eye tracking performance and attention in alcohol abusers and psychotic patients. In: Gale AG, Johnson F (eds) Theoretical and applied aspects of eye movement research. Elsevier Science Publishers, North Holland, pp 489–496

    Google Scholar 

  • Aschan G (1958) Different types of alcohol nystagmus. Acta Otolaryngol Suppl 140: 69–78

    Google Scholar 

  • Aschan G, Bergstedt M, Stahle J (1956) Nistagmography: recording of nystagmus in clinical neuro-otological examinations. Acta Otolaringol Suppl 129: 1–103

    Google Scholar 

  • Bahill AT, Stark L (1975) Overlapping saccades and glissades are produced by fatigue in the saccadic eye movements system. Exp Neurol 48: 95–106

    Google Scholar 

  • Bahill AT, Clark MR, Stark L (1975) Glissades-eye movements generated by mismatched components of the saccadic motoneuronal control signal. Math Biosci 26: 303–318

    Google Scholar 

  • Barnes GR (1984) The effects of ethyl alcohol on visual pursuit and suppression of vestibulo-ocular reflex. Acta Otolaryngol Suppl 406: 161–166

    Google Scholar 

  • Biggio G, Guidotti A (1976) Climbing fiber activation and 3′,5′ cyclic guanosine monophosphate (cGMP) content in cortex and deep nuclei of the cerebelellum. Brain Res 107: 365–373

    Google Scholar 

  • Bixler MA, Lewis MJ (1987) The partial inverse benzodiazepine agonist Ro 15-4513 potentiates ethanol induced suppression of wheel running in the rat. Soc Neurosci Abstr 13: 967

    Google Scholar 

  • Bonetti EP, Polc P, Pieri L (1984) An azido analogue of the benzodiazepine antagonist Ro 15-1788 (Ro 15-4513) behaves as a partial inverse benzodiazepine agonist. Neurosci Lett Suppl 18: S30

    Google Scholar 

  • Bonetti EP, Burkard WP, Gabl M, Möhler H (1985) The partial inverse benzodiazepine agonist Ro 15-4513 antagonizes acute ethanol effects in mice and rats. Br J Pharmacol 86: 463P

  • Britton KT, Ehlers CL, Koob GF (1988) Is ethanol antagonist Ro 15-4513 selective for ethanol? Science 239: 648–649

    Google Scholar 

  • Chelazzi L, Rossi F, Tempia F, Ghirardi M, Strata P (1988) Spontaneous saccades in the rat following localized cerebellar lesions. Eur J Neurosci Suppl, p 7

  • Dichgans J (1984) Clinical symptoms of cerebellar dysfunction and their topodiagnostical significance. Human Neurobiol 2: 269–279

    Google Scholar 

  • Dodge R, Benedict FG (1915) Psychological effects of alcohol. The Carnegie Institution of Washington, Washington D.C.

    Google Scholar 

  • Ehlers CL, Ian Chaplin R, Koob GF (1987) RO 15-4513 and FG 7142 antagonize the EEG effects of ethanol but also produce limbic seizure activity. Soc Neurosci Abstr 13: 503

    Google Scholar 

  • Flom MC, Brown B, Adams AJ, Jones RT (1976) Alcohol and marijuana effects on ocular tracking. Am J Optom Physiol Opt 53: 764–773

    Google Scholar 

  • Franck MC, Kuhlo W (1970) Die Wirkung des Alhohols auf die raschen Blickzielbewegungen (Saccaden) beim Menschen. Arch Psychiatr Nervenkr 213: 238–245

    Google Scholar 

  • Fuchs AF, Luschei ES (1970) Firing patterns of abducens neurons of alert monkeys in relationship to horizontal eye movement. J Neurophysiol 33: 382–392

    Google Scholar 

  • Goding GS, Dobie RA (1986) Gaze nystagmus and blood alcohol. Laryngoscope 96: 713–717

    Google Scholar 

  • Guedry FE Jr, Gilson RD, Schroeder DJ, Collins WE (1975) Some effects of alcohol on various aspects of oculomotor control. Aviat Space Environ Med 46(8): 1008–1013

    Google Scholar 

  • Guidotti A, Biggio G, Costa E (1975) 3-acetylpyridine: a tool to inhibit the tremor and the increase of cGMP content in cerebellar cortex elicited by harmaline. Brain Res 96: 201–205

    Google Scholar 

  • Hess BJM, Savio T, Strata P (1988) Dynamic characteristics of optokinetically controlled eye movements following inferior olive lesions in the brown rat. J Physiol (Lond) 397: 349–370

    Google Scholar 

  • Kasper HJ, Hess BJM, Dieringer N (1987) A precise and inexpensive magnetic field search coil system for measuring eye and head movements in small laboratory animals. J Neurosci Meth 19: 115–124

    Google Scholar 

  • Kolata G (1986) New drug counters alcohol intoxication. Science 234: 1198–1199

    Google Scholar 

  • Kommerell G, Olivier D, Theopold H (1976) Adaptive programming of phasic and tonic components in saccadic eye movements: investigations in patients with abducens palsy. Invest Opthalmol 15: 657–660

    Google Scholar 

  • Lehti H (1976) The effect of blood alcohol concentration on the onset of gaze nystagmus. Blutalkohol 13: 411–414

    Google Scholar 

  • Leigh RJ, Zee DS (1983) The neurology of eye movements. F A Davis Company, Philadelphia

    Google Scholar 

  • Lister RG (1987a) The benzodiazepine receptor inverse agonists FG 7142 and Ro 15-4513 both reverse some of the behavioural effects of ethanol in the holeboard test. Life Sci 41: 1481–1489

    CAS  PubMed  Google Scholar 

  • Lister RG (1987b) Interactions of Ro 15-4513 with diazepam, sodium pentobarbital and ethanol in the holeboard test. Pharmacol Biochem Behav 28: 75–79

    Google Scholar 

  • Lister RG, Karanian JW (1987) Ro 15-4513 induces seizures in DBA/2 mice undergoing alcohol withdrawal. Alcohol 4: 409–411

    Google Scholar 

  • Lister RG, Nutt DJ (1987) Is Ro 15-4513 a specific alcohol antagonist? Trends Neurosci 10: 223–225

    Google Scholar 

  • Lister RG, Nutt DJ (1988) Interactions of the imidazobenzodiazepine Ro 15-4513 with chemical convulsants. Br J Pharmacol 93(1): 210–214

    Google Scholar 

  • Mailman RB, Frye GD, Mueller RA, Breese GR (1978) Thyrotropin releasing hormone reversal of ethanol-induced decreases in cerebellar cGMP. Nature (Lond) 272: 832–833

    Google Scholar 

  • Mereu GP, Passino N, Diana M, Marrosu P, Aramo S, Gessa GL (1987) Effect of Ro 15-4513 on nigral-pars reticulata neurons. Soc Neurosci Abstr 13: 572

    Google Scholar 

  • Miczek KA, Weerts EM (1987) Seizures in drug treated animals. Science 235: 1127

    Google Scholar 

  • Miles WR (1924) Alcohol and human efficiency. The Carnegie Institution of Washington, Washington DC

    Google Scholar 

  • Moore EA, Palmer MR (1987) Antagonism of ethanol-induced depressions of cerebellar Purkinje neurons in rats with the benzodiazepine Ro 15-4513. Soc Neurosci Abstr 13: 503

    Google Scholar 

  • Nestoros JN (1980) Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex. Science 209: 708–710

    Google Scholar 

  • Optican LM, Robinson DA (1980) Cerebellar-dependent adaptive control of primate saccadic system. J Neurophysiol 44: 1058–1075

    Google Scholar 

  • Pallestrini EA, Accomanno E, Borasi F, Garaventa G (1985) Interferenze farmacologiche nello studio dei movimenti oculari di interesse otoneurologico. Oto-Rino-Laring 35: 549–557

    Google Scholar 

  • Polc P (1985) Interactions of partial inverse benzodiazepine agonist Ro 15-4513 and FG 7142 with ethanol in rats and cats. Br J Pharmacol 86: 465P

  • Redos JD, Catravas GN, Hunt WA (1976) Ethanol-induced depletion of cerebellar guanosine 3′,5′-cyclic monophosphate. Science 193: 58–59

    Google Scholar 

  • Robinson DA (1964) The mechanics of human saccadic eye movements. J Physiol (Lond) 174: 245–264

    Google Scholar 

  • Robinson DA (1970) Oculomotor unit behavior in the monkey. J Neurophysiol 33: 393–404

    Google Scholar 

  • Robinson DA (1975) Oculomotor control signals. In: Bach-y-Rita P, Lennerstrand G (eds) Basic mechanisms of ocular motility and their clinical implications. Pergamon, Oxford, pp 337–374

    Google Scholar 

  • Rogers J, Siggins GR, Schulman JA, Bloom FE (1980) Physiological correlates of ethanol intoxication, tolerance and dependence in rat cerebellar Purkinje cells. Brain Res 196: 183–198

    Google Scholar 

  • Rossi F, Chelazzi L, Tempia F, Strata P (1988) Antagonist action of imidazobenzodiazepine Ro 15-4513 on ethanol-induced alterations of saccadic eye movements in the pigmented rat. Neurosci Lett 89: 69–73

    Google Scholar 

  • Sinclair JG, Lo GF, Harris DP (1982) Ethanol effects on the olivocerebellar system. Can J Physiol Pharmacol 60: 610–614

    Google Scholar 

  • Suzdak P, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM (1986) A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 234: 1243–1247

    Google Scholar 

  • Tempia F, Chelazzi L, Rossi F, Ghirardi M, Strata P (1989) Spontaneous saccades in the pigmented rat after inferior olive lesion. In: Strata P (ed) The olivocerebellar system in motor control. Exp Brain Res series 17: 294–298

  • Turner DM, Olsen RW (1987) Characterization of the benzodiazepine/alcohol antagonist Ro 15-4513 binding sites in the cerebellum. Soc Neurosci Abstr 13: 962

    Google Scholar 

  • Umeda Y, Sakata E (1978) Alcohol and the oculomotor system. Ann Otol 87: 392–398

    Google Scholar 

  • Weber RB, Daroff RB (1972) Corrective movements following refixation saccades: type and control system analysis. Vision Res 12: 467–475

    Google Scholar 

  • Wilkinson IMS, Kime R, Purnell M (1974) Alcohol and human eye movements. Brain 97: 785–792

    Google Scholar 

  • Zee DS, Yamazaki A, Butler PH, Güçer G (1981) Effects of ablation of flocculus and paraflocculus on eye movements in primate. J Neurophysiol 46: 878–899

    Google Scholar 

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Rossi, F., Chelazzi, L., Tempia, F. et al. Effects of ethanol and imidazobenzodiazepine Ro 15-4513 on spontaneous saccades of the pigmented rat. Exp Brain Res 76, 1–11 (1989). https://doi.org/10.1007/BF00253617

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  • DOI: https://doi.org/10.1007/BF00253617

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