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Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task

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Abstract

Rationale

Several studies have shown the amnestic effects of ethanol (ETOH). However, while memory tasks in rodents can be markedly influenced by anxiety-like behavior and motor function, ETOH induces anxiolysis and different effects on locomotion, depending on the dose.

Objective

Verify the effects of ETOH in mice tested in the plus-maze discriminative avoidance task (PMDAT) concomitantly evaluating memory, anxiety-like behavior, and motor behavior.

Methods

ETOH acutely or repeatedly treated mice were submitted to the training session in a modified elevated plus-maze with two open and two enclosed arms, aversive stimuli in one of the enclosed arms, and tested 24 h later without aversive stimuli. Learning/memory, locomotion, and anxiety-related behavior were evaluated by aversive arm exploration, number of entries in all the arms and open arms exploration, respectively.

Results

Acute ETOH: (1) either increased (1.2–1.8 g/kg) or decreased (3.0 g/kg) locomotion; (2) decreased anxiety levels (1.2–3.0 g/kg); and (3) induced learning deficits (1.2–3.0 g/kg) and memory deficits (0.3–3.0 g/kg). After repeated treatment, sensitization and tolerance to hyperlocomotion and anxiolysis induced by 1.8 g/kg ETOH were observed, respectively, and tolerance to the amnestic effect of 0.6 (but not 1.8) g/kg ETOH occurred.

Conclusion

Neither the anxiolytic nor the locomotor effects of ETOH seem to be related to its amnestic effect in the PMDAT. Additionally, data give support to the effectiveness of the PMDAT in simultaneously evaluating learning, memory, anxiety-like behavior, and motor activity by different parameters. Possible relationships between the behavioral alterations found are discussed.

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References

  • Araujo NP, Andersen ML, Abilio VC, Gomes DC, Carvalho RC, Silva RH, Ribeiro RdA, Tufik S, Frussa-Filho R (2006) Sleep deprivation abolishes the locomotor stimulant effect of ETOH in mice. Brain Res Bull 69:332–337

    Article  PubMed  CAS  Google Scholar 

  • Bammer G, Chesher GB (1982) An analysis of some effects of ETOH on performance in a passive avoidance task. Psychopharmacology 77:66–73

    Article  PubMed  CAS  Google Scholar 

  • Bellot RG, Camarini R, Vital MABF, Palermo-Neto J, Leyton V, Frussa-Filho R (1996) Monosialoganglioside attenuates the excitatory and behavioural sensitization effects of ETOH. Eur J Pharmacol 313:175–179

    Article  PubMed  CAS  Google Scholar 

  • Bertoglio LJ, Carobrez AP (2002) Anxiolytic effects of ETOH and Phenobarbital are abolished in test-experienced rats submitted to the elevated plus maze. Pharmacol Biochem Behav 73:963–969

    Article  PubMed  CAS  Google Scholar 

  • Boulouard M, Lelong V, Daoust M, Naassila M (2002) Chronic ETOH consumption induces tolerance to the spatial memory impairing effects of acute ETOH administration in rats. Behav Brain Res 136:239–246

    Article  PubMed  CAS  Google Scholar 

  • Claro FT, Silva RH, Frussa-Filho R (1999) Bovine brain phosphatidylserine attenuates scopolamine induced amnesia. Physiol Behav 67:551–554

    Article  PubMed  CAS  Google Scholar 

  • Cohen C, Perrault GH, Sanger DJ (1997) Evidence for the involvement of dopamine receptors in ethanol-induced hyperactivity in mice. Neuropharmacology 36:1099–1108

    Article  PubMed  CAS  Google Scholar 

  • Cole JC, Littleton JM, Little HJ (1999) Effects of repeated ETOH administration in the plus maze; a simple model for conditioned abstinence behaviour. Psychopharmacology 142:270–279

    Article  PubMed  CAS  Google Scholar 

  • Crabbe JC, Johnson NA, Gray DK, Kosobud A, Young ER (1982) Biphasic effects of ETOH on open-field activity: sensitivity and tolerance in C57BL/6N and DBA/2N mice. J Comp Physiol Psychol 96:440–451

    Article  PubMed  CAS  Google Scholar 

  • Cunningham CL, Noble D (1992) Conditioned activation induced by ETOH: role in sensitization and conditioned place preference. Pharmacol Biochem Behav 43:307–313

    Article  PubMed  CAS  Google Scholar 

  • Escher T, Mittleman G (2004) Effects of ETOH and GABA B drugs on working memory in C57BL/6J and DBA/2J mice. Psychopharmacology 176:166–174

    Article  PubMed  CAS  Google Scholar 

  • File SE, Mabbutt PS (1990) Long-lasting effects on habituation and passive avoidance performance of a period of chronic ETOH administration in the rat. Behav Brain Res 36:171–178

    Article  PubMed  CAS  Google Scholar 

  • Franke H, Kittner H, Berger P, Wirckner K, Schrameck J (1997) The reaction of astrocytes in neurons in the hippocampus of adult rats during chronic ETOH treatment and correlations to behavioral impairments. Alcohol 14:445–454

    Article  PubMed  CAS  Google Scholar 

  • Frussa-Filho R, Goncalves MT, Andersen ML, de Araujo NP, Chinen CC, Tufik S (2004) Paradoxical sleep deprivation potentiates amphetamine-induced behavioural sensitization by increasing its conditioned component. Brain Res 1003:188–193

    Article  PubMed  CAS  Google Scholar 

  • Gallate JE, Morley KC, Ambermoon P, McGregor IS (2003) The consequences of beer consumption in rats: acute anxiolytic and ataxic effects and withdrawal-induced anxiety. Psychopharmacology 166:51–60

    PubMed  CAS  Google Scholar 

  • Gibson WE (1985) Effects of alcohol on radial maze performance in rats. Physiol Behav 35:1003–1005

    Article  PubMed  CAS  Google Scholar 

  • Givens B (1995) Low doses of ETOH impair spatial working memory and reduce hippocampal theta activity. Alcohol Clin Exp Res 19:763–767

    Article  PubMed  CAS  Google Scholar 

  • Givens B, McMahon K (1997) Effects of ETOH on nonspatial working memory and attention in rats. Behav Neurosci 111:275–282

    Article  PubMed  CAS  Google Scholar 

  • Gonenc S, Uysal N, Acikgoz O, Kayatekin BM, Sonmez A, Kiray M, Aksu I, Gulecer B, Topcu A, Semin I (2005) Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ETOH treatment in rats. Physiol Res 54:341–348

    PubMed  CAS  Google Scholar 

  • Gould TJ (2003) ETOH disrupts fear conditioning in C57BL/6 mice. J Psychopharmacol 17:77–81

    Article  PubMed  CAS  Google Scholar 

  • Harper C, Matsumoto I (2005) ETOH and brain damage. Curr Opin Pharmacol 5:73–78

    Article  PubMed  CAS  Google Scholar 

  • Korbo L (1999) Glial cell loss in the hippocampus of alcoholics. Alcohol Clin Exp Res 23(1):164–168

    PubMed  CAS  Google Scholar 

  • Land C, Spear NE (2004) Fear conditioning is impaired in adult rats by ETOH doses that do not affect periadolescents. Int J Dev Neurosci 22:355–362

    Article  PubMed  CAS  Google Scholar 

  • Levitan IB, Kaczmarek LK (1991) Learning and memory. In: Levitan IB, Kaczmarek LK (eds) The neuron: cell and molecular biology. Oxford University Press, Oxford, pp 395–423

    Google Scholar 

  • Lukoyanov NV, Madeira MD, Paula-Barbosa MM (1999) Behavioral and neuroanatomical consequences of chronic ETOH intake and withdrawal. Physiol Behav 66:337–346

    Article  PubMed  CAS  Google Scholar 

  • Markel E, Nyakas C, Tal E, Endroczi E (1986) Changes in avoidance behaviour following ETOH treatment in rats of different ages. Physiol Hung 68(2):175–181

    CAS  Google Scholar 

  • Masur J, Souza MLO, Zwicker AP (1986) The excitatory effect of ETOH: absence in rats, no tolerance and increased sensitivity in mice. Pharmacol Biochem Behav 24:1225–1228

    Article  PubMed  CAS  Google Scholar 

  • Mathews A (1990) Why worry? The cognitive function of anxiety. Behav Res Ther 28:455–468

    Article  PubMed  CAS  Google Scholar 

  • Matthews DB, Simson PE, Best PJ (1995) Acute ETOH impairs spatial memory but not stimulus/response memory in the rat. Alcohol Clin Exp Res 19:902–909

    Article  PubMed  CAS  Google Scholar 

  • Matthews DB, Morrow AL, Tokunaga S, McDaniel JR (2002) Acute ETOH administration and acute allopregnanolone administration impair spatial memory in the Morris water task. Alcohol Clin Exp Res 26:1747–1751

    PubMed  CAS  Google Scholar 

  • Melchior CL, Glasky AJ, Ritzmann RF (1993) A low dose of ETOH impairs working memory in mice in a winshift foraging paradigm. Alcohol 10:491–493

    Article  PubMed  CAS  Google Scholar 

  • Melis F, Stancampiano R, Imperato A, Carta G, Fadda F (1996) Chronic ETOH consumption in rats: correlation between memory performance and hippocampal acetylcholine release in vivo. Neuroscience 74:155–159

    Article  PubMed  CAS  Google Scholar 

  • Moser PC (1989) An evaluation of the elevated plus-maze test using the novel anxiolytic buspirone. Psychopharmacology 99(1):48–53

    Article  PubMed  CAS  Google Scholar 

  • Naylor JC, Simson PE, Gibson B, Schneider AM, Wilkins E, Firestone A, Choy M (2001) ETOH inhibits spontaneous activity of central nucleus of the amygdala neurons but doe not impair retention in the passive-avoidance task. Alcohol Clin Exp Res 25(11):1683–1688

    Article  PubMed  CAS  Google Scholar 

  • Patti CL, Kameda SR, Carvalho RC, Takatsu-Coleman AL, Lopez GB, Niigaki ST, Abilio VC, Frussa-Filho R, Silva RH (2006) Effects of morphine on the plus-maze discriminative avoidance task: role of state-dependent learning. Psychopharmacology 184:1–12

    Article  PubMed  CAS  Google Scholar 

  • Phillips KM (1982) Effects of time and administration of ETOH on open-field behavior in hamsters. Physiol Behav 29:785–787

    Article  PubMed  CAS  Google Scholar 

  • Popovic M, Caballero-Bleda M, Puelles L, Guerri C (2004) Multiple binge alcohol consumption during rat adolescence increases anxiety but does not impair retention in the passive avoidance task. Neuroscience 357:779–782

    Google Scholar 

  • Prediger RD, Takahashi RN (2003) ETOH improves short-term social memory in rats involvement of opioid and muscarinic receptors. Eur J Pharmacol 462:115–123

    Article  PubMed  CAS  Google Scholar 

  • Rajendran P, Spear LP (2004) The effects of ETOH on spatial and nonspatial memory in adolescent and adult rats studied using an appetitive paradigm. Ann N Y Acad Sci 1021:441–444

    Article  PubMed  CAS  Google Scholar 

  • Rossetti ZL, Carboni S, Stancampiano R, Sori P, Pepeu G, Fadda F (2002) Bidirectional modulation of spatial working memory by ETOH. Alcohol Clin Exp Res 26:181–185

    PubMed  CAS  Google Scholar 

  • Silva RH, Frussa-Filho R (2000) The plus-maze discriminative avoidance task: a new model to study memory-anxiety interactions. Effects chlordiazepoxide and caffeine. J Neurosci Methods 102:117–125

    Article  PubMed  CAS  Google Scholar 

  • Silva RH, Bellot RG, Vital MABF, Frussa-Filho R (1997) Effects of long-term ganglioside GM1 administration on a new discriminative avoidance test in normal adult mice. Psychopharmacology 129:322–328

    PubMed  CAS  Google Scholar 

  • Silva RH, Felício LF, Frussa-Filho R (1999) Ganglioside GM1 attenuates scopolamine-induced amnésia. Psychopharmacology 141:111–117

    Article  PubMed  CAS  Google Scholar 

  • Silva RH, Kameda SR, Carvalho RC, Rigo GS, Costa KLB, Taricano ID, Frussa-Filho R (2002a) Effects of amphetamine on the plus-maze discriminative avoidance task in mice. Psychopharmacology 160:9–18

    Article  CAS  Google Scholar 

  • Silva RH, Abílio VC, Torres-Leite D, Bergamo M, Chinen CC, Claro FT, Carvalho RC, Frussa-Filho R (2002b) Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice. Behav Brain Res 132:171–177

    Article  CAS  Google Scholar 

  • Silva RH, Abílio VC, Kameda SR, Takatsu-Coleman AL, Carvalho RC, Ribeiro R de A, Tufik S, Frussa-Filho R (2006) Effects of 3-nitropropionic acid administration on memory and hippocampal lipid peroxidation in sleep-deprived mice. Prog Neuropsychopharmacol Biol Psychiat DOI 10.1016/j.pnpbp.2006.06.019

  • Silvestre JS, Pallares M, Nadal R, Ferre N (2002) Opposite effects of ETOH and ketamine in the elevated plus-maze test in Wistar rats undergoing a chronic oral voluntary consumption procedure. J Psychopharmacol 16:305–312

    Article  PubMed  CAS  Google Scholar 

  • Singh A, Naidu PS, Kulkarni SK (2003) Reversal of aging and chronic ETOH-induced cognitive dysfunction by quercetin a bioflavonoid. Free Radic Res 37:1245–1252

    Article  PubMed  CAS  Google Scholar 

  • Steigerwald ES, Miller MW (1997) Perfomance by adult rats in sensory-mediated radial arm maze tasks is not impaired and may be transiently enhanced by chronic exposure to ETOH. Alcohol Clin Exp Res 21:1553–1559

    PubMed  CAS  Google Scholar 

  • Vanderschuren LJMJ, Schmidt ED, De Vries TJ, Van Moorsel CAP, Tilders FJH, Schoffelmeer ANM (1999) A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine and neurochemical sensitization in rats. J Neurosci 19:9579–9586

    PubMed  CAS  Google Scholar 

  • Varlynskaya EI, Spear LP (2002) Acute effects of ethanol on social behavior of adolescent and adult rats: role of familiarity of the test situation. Alcohol Clin Exp Res 26:1502–1511

    Google Scholar 

  • Weitemier AZ, Ryabinin AE (2003) Alcohol-induced memory impairment in trace fear conditioning: a hippocampus-specific effect. Hippocampus 13:305–315

    Article  PubMed  CAS  Google Scholar 

  • Whener JM, Keller JJ, Keller AB, Picciotto MR, Paylor R, Booker TK, Beaudet A, Heinemann SF, Balogh SA (2004) Role of neuronal nicotinic receptors in the effects of nicotine and ETOH on contextual fear conditioning. Neuroscience 129:11–24

    Article  CAS  Google Scholar 

  • White AM, Simson PE, Best PJ (1997) Comparison between the effects of ETOH and diazepam on spatial working memory in the rat. Psychopharmacology 133:256–261

    Article  PubMed  CAS  Google Scholar 

  • Wilson MA, Burghardt PR, Ford KA, Wilkinson MB, Primeaux SD (2004) Anxiolytic effects of diazepam and ETOH in two behavioral models: comparison of males and females. Pharmacol Biochem Behav 78:445–458

    Article  PubMed  CAS  Google Scholar 

  • Wright JW, Masino AJ, Reichert JR, Turner GD, Meighan SE, Meighan PC, Harding JW (2003) ETOH-induced impairment of spatial memory and brain matrix metalloproteinases. Brain Res 963:252–261

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Ms. Teotila R. R. Amaral, Mr. Cleomar S. Ferreira and Mr. Antonio R. dos Santos for capable technical assistance. This research was supported by fellowships from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), from Fundo de Auxílio ao Docente e Aluno da UNIFESP (FADA), from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 305029/2004-5), and from Associação Fundo de Incentivo à Psicofarmacologia (AFIP).

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Correspondence to R. H. Silva.

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Kameda, S.R., Frussa-Filho, R., Carvalho, R.C. et al. Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task. Psychopharmacology 192, 39–48 (2007). https://doi.org/10.1007/s00213-006-0684-9

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  • DOI: https://doi.org/10.1007/s00213-006-0684-9

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