Abstract
The elevated plus maze (EPM) is an animal model of anxiety used to test the effects of anxioselective drugs. The loss of the anxiolytic effect of drugs during the second exposure to the EPM is called the “one trial tolerance” (OTT) phenomenon. The present study was designed to investigate the relationship between the OTT phenomenon and N-methyl-d-aspartate (NMDA) receptor blockade in the early developmental period of rats. NMDA receptor blockade was accomplished using MK-801 treatment given between postnatal days 20–30. Beginning on postnatal day 20, the rats were subcutaneously injected with MK-801 twice a day at the nape of the neck for a period of 10 days (0.25 mg/kg). Increased open arm exploration was observed in MK-801-treated rats during trial 1 (p = 0.001) and trial 2 (p = 0.003). The rats spent less time in the closed arms as compared to the saline animals in trial 1 (p = 0.006), and this time decreased further in trial 2 (p = 0.02). The fecal boli of the MK-801 group was decreased in trial 1 as compared to the saline group (p = 0.01), but was not significantly different in trial 2 (p = 0.08). In conclusion, NMDA receptor blockade using MK-801 produced an anxiolytic-like effect in trials 1 and 2. Furthermore, OTT was not affected by NMDA receptor blockade.
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Bessa JM, Oliveira M, Cerqueira JJ, Almeida OF, Sousa N (2005) Age-related qualitative shift in emotional behaviour: paradoxical findings after re-exposure of rats in the elevated-plus maze. Behav Brain Res 162(1):135–142
Rodgers RJ, Cole JC (1994) The elevated plus-maze: pharmacology, methodology and ethology. In: Cooper SJ, Hendrie CA (eds) Ethology and psychopharmacology. Wiley, Chichester, pp 9–44
Dal-Col MC, Pereira LO, Rosa VP, Calixto AV, Carobrez AP, Faria MS (2003) Lack of midazolam-induced anxiolysis in the plus-maze trial 2 is dependent on the length of trial 1. Pharmacol Biochem Behav 74(2):395–400
Roy V, Chapillon P, Jeljeli M, Caston J, Belzung C (2009) Free versus forced exposure to an elevated plus-maze: evidence for new behavioral interpretations during test and retest. Psychopharmacology 203(1):131–141
File SE, Mabbutt PS, Hitchcott PK (1990) Characterisation of the phenomenon of “one-trial tolerance” to the anxiolytic effect of chlordiazepoxide in the elevated plus-maze. Psychopharmacology 102:98–101
Bertoglio LJ, Carobrez AP (2003) Anxiolytic-like effects of NMDA/glycine-B receptor ligands are abolished during the elevated plus-maze trial 2 in rats. Psychopharmacology 170:335–342
Mitra R, Vyas A, Chatterjee C, Chattarji S (2005) Chronic-stress induced modulation of different states of anxiety-like behavior in female rats. Neurosci Lett 383(3):278–283
Andersen SL (2003) Trajectories of brain development: point of vulnerability or window of opportunity? Neurosci Biobehav Rev 27:3–18
Holmes A, Guisque AM, Vogel E, Millstein RA, Leman S, Belzung C (2005) Early life genetic, epigenetic and environmental factors shaping emotionality in rodents. Neurosci Biobehav Rev 29:1335–1346
Jentsch JD, Roth RH (1999) The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20:201–225
Kocahan S, Babar E, Melik E, Akillioglu K (2012) The effect of interaction between N-methyl-d-aspartate receptor blockade and growth environment during the last maturation period of the nervous system on anxiety-related behaviour in adulthood in the rat. Neurochem J 6(3):194–201
Mutlu O, Ulak G, Celikyurt IK, Akar FK, Erden F, Tanyeri P (2011) Effects of olanzapine, sertindole and clozapine on MK-801 induced visual memory deficits in mice. Pharmacol Biochem Behav 99:557–565
Gorter JA, Botterblom MH, Feenstra MG, Boer GJ (1992) Chronic neonatal NMDAreceptor blockade with MK-801 alters monoamine metabolism in the adult rat. Neurosci Lett 137:97–100
Gorter JA, Veerman M, Mirmiran M (1992) Hippocampal neuronal responsiveness to NMDAagonists and antagonists in the adult rat neonatally treated withMK-801. Brain Res 572:176–181
Wang C, McInnis J, Ross-Sanchez M, Shinnick-Gallagher P, Wiley JL, Johnson KM (2001) Long-term behavioral and neurodegenerative effects of perinatal phencyclidine administration: implications for schizophrenia. Neuroscience 107:535–550
Baier PC, Blume A, Koch J, Marx A, Fritzer G, Aldenhoff JB, Schiffelholz T (2009) Early postnatal depletion of NMDA receptor development affects behaviour and NMDA receptor expression until later adulthood in rats—a possible model for schizophrenia. Behav Brain Res 205:96–101
Fraser CM, Cooke MJ, Fisher A, Thompson ID, Stone TW (1996) Interactions between ifenprodil and dizocilpine on mouse behaviour in models of anxiety and working memory. Eur Neuropsychopharmacol 6:311–316
Kocahan S, Akillioglu K, Binokay S, Polat S, Sencar L (2013) The effects of N-methyl-d-aspartate receptor blockade during the early neurodevelopmental period on emotional behaviors and cognitive functions of adolescent wistar rats. Neurochem Res. doi:10.1007/s11064-013-1008-1
Li JT, Su YA, Guo CM, Feng Y, Yang Y, Huang RH, Si TM (2011) Persisting cognitive deficits induced by low-dose, subchronic treatment with MK-801in adolescent rats. Eur J Pharmacol 652:65–72
Baier PC, Blume A, Koch J, Marx A, Fritzer G, Aldenhoff JB, Schiffelholz T (2009) Early postnatal depletion of NMDA receptor development affects behaviour and NMDA receptor expression until later adulthood in rats—a possible model for schizophrenia. Behav Brain Res 205:96–101
Enomoto T, Floresco SB (2009) Disruptions in spatial working memory, but not short-term memory, induced by repeated ketamine exposure. Prog Neuropsychopharmacol Biol Psychiatry 33:668–675
Uehara T, Sumiyoshi T, Seo T, Matsuoka T, Itoh H, Suzuki M, Kurachi M (2010) Neonatal exposure to MK-801, an N-methyl-d-aspartate receptor antagonist, enhances methamphetamine-induced locomotion and disrupts sensorimotor gating in pre- and post-pubertal rats. Brain Res 17:223–230
Stefani MR, Moghaddam B (2005) Transient N-methyl-d-aspartate receptor blockade in early development causes lasting cognitive deficits relevant to schizophrenia. Biol Psychiatry 57:433–436
Schiffelholz T, Hinze-Selch D, Aldenhoff JB (2004) Perinatal MK-801 treatment affects age-related changes in locomotor activity from childhood to later adulthood in rats. Neurosci Lett 360:157–160
Denenberg V (1969) Open-field behaviour in the rat: what does it mean? Ann N Y Acad Sci 159:852–859
Gorman JM, Kent JM, Sullivan GM, Coplan JD (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505
Akillioglu K, Binokay S, Kocahan S (2012) The effect of neonatal N-methyl-d-aspartate receptor blockade on exploratory and anxiety-like behaviors in adult BALB/c and C57BL/6 mice. Behav Brain Res 233(1):157–161
Dunn RW, Corbett R, Fielding S (1989) Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze. Eur J Pharmacol 169:1–10
Gray JA, McNaughton N (2000) The neuropsychology of anxiety, 1st edn. Oxford University Press, Oxford
Dawson GR, Crawford SP, Stanhope KJ, Iversen SD, Tricklebank MD (1994) One-trial tolerance to the effects of chlordiazepoxide on the elevated plus maze may be due to locomotor habituation, not repeated drug exposure. Psychopharmacology 113:570–572
Bertoglio LJ, Carobrez AP (2002) Anxiolytic effects of ethanol and phenobarbital are abolished in test-experienced rats submitted to the elevated plus maze. Pharmacol Biochem Behav 73:963–969
Bertoglio LJ, Carobrez AP (2002) Behavioral profile of rats submitted to session 1–session 2 in the elevated plus-maze during diurnal/nocturnal phases and under different illumination conditions. Behav Brain Res 132:135–143
Bertoglio LJ, Carobrez AP (2002) Prior maze experience required to alter midazolam effects in rats submitted to the elevated plusmaze. Pharmacol Biochem Behav 72:449–455
Cruz-Morales SE, Santos NR, Brand ML (2002) One-trial tolerance to midazolam is due to enhancement of fear and reduction of anxiolytic-sensitive behaviors in the elevated plusmaze retest in the rat. Pharmacol Biochem Behav 72:973–978
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Kocahan, S., Akillioglu, K. Effects of NMDA Receptor Blockade During the Early Development Period on the Retest Performance of Adult Wistar Rats in the Elevated Plus Maze. Neurochem Res 38, 1496–1500 (2013). https://doi.org/10.1007/s11064-013-1051-y
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DOI: https://doi.org/10.1007/s11064-013-1051-y