Abstract
This study examined the effects of the benzodiazepine agonist midazolam and inverse agonist noreleagnine independently and in conjunction with the antagonist flumazenil in the mouse staircase test. According to this paradigm, the numbers of steps ascended (NSA) and rears (NR) reflect locomotor activity and anxiety, respectively. Midazolam reduced NR at doses that did not affect NSA; this NR-lowering effect was blocked by flumazenil. Noreleagnine increased NR at doses that did not affect NSA; this NR-elevating effect was also blocked by flumazenil. Effective antagonist doses of flumazenil alone had no effect on NR or NSA. The exactly opposite effects of midazolam and noreleagnine on NR and their antagonism by flumazenil are consistent with the postulated activities of these drugs at benzodiazepine receptors.
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References
Belzung C, Misslin R, Vogel E, Dodd RH, Chapouthier G (1987) Anxiogenic effects of methy-β-carboline-3-carboxylate in a light/dark choice situation. Pharmacol Biochem Behav 28:29–33
Belzung C, Misslin R, Vogel E (1988) The benzodiazepine receptor inverse agonists β-CCM and RO 15-3505 both reverse the anxiolytic effects of ethanol in mice. Life Sci 42:1765–1772
Braestrup C, Nielsen M, Honore T, Jensen LH, Petersen EN (1983) Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology 22:1451–1457
Keane PL, Simiand J, Morre M, Biziere K (1988) Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. I. Psychopharmacological profile in rodents. J Pharmacol Exp Ther 245:692–698
Lal H, Shearman GT, Fielding S, Dunn R, Kruse M, Theurer K (1980) Evidence that GABA mechanisms mediate the anxiolytic action of benzodiazepines: a study with valproic acid. Neuropharmacology 19:785–789
Misslin R, Ropartz P, Mandel P (1975) Etude comparée du di-n-propylacétate et de l'oxazépam sur l'activité spontanée de la souris. CR Acad Sci III 281:1175–1178
Ohmori K, Yamanami S, Shuto K, Marumo H (1980) Effect of sodium dipropylacetate on conflict behavior in rats. Jpn J Pharmacol 30:925–927
Olsen RW (1982) Drug interactions at the GABA receptor-ionophore complex. Annu Rev Pharmacol Toxicol 22:245–277
Pollard GT, Howard JL (1986) The staircase test: some evidence of nonspecificity for anxiolytics. Psychopharmacology 89:14–19
Porsolt RD, Lenégre A, Avril I, Doumont G (1988) Antagonism by exifone, a new cognitive enhancing agent, of the amnesias induced by four benzodiazepines in mice. Psychopharmacology 95:291–297
Pruhs RJ, Kalbfleisch JH, Quock RM (1988) Combination effects of chloral hydrate and nitrous oxide/oxygen in the mouse staircase test. Anesth Prog 35:116–120
Pruhs RJ, Quock RM (1989) Interaction between nitrous oxide and diazepam in the mouse staircase test. Anesth Analg 68:501–505
Quock RM, Wojcechowskyj JA, Emmanouil DE (1987) Comparison of nitrous oxide, morphine and diazepam effects in the mouse staircase test. Psychopharmacology 92:324–326
Shekhar A, Hingtgen JN, DiMicco JA (1989) Anxiogenic effects of noreleagnine, a water soluble beta-carboline in rats. Neuropharmacology 28:539–542
Simiand J, Keane PE, Morre M (1984) The staircase test in mice: a simple and efficient procedure for primary screening of anxiolytic agents. Psychopharmacology 84:48–53
Stéru L, Thierry B, Chermat R, Millet B, Simon P, Porsolt RD (1987) Comparing benzodiazepines using the staircase test in mice. Psychopharmacology 92:106–109
Thiébot MH, Soubrié P, Simon P, Boissier JR (1973) Dissociation de deux composantes du comportement chez le rat sous l'effet de psychotropes. Application a l'étude des anxiolytiques. Psychopharmacologia 31:77–90
Thiébot MH, Sourbrié P, Simon P, Boissier JR (1976) Specificité d'action des tranquillisants mineurs dans le test de l'escalier. Relation entre ces effets et leurs propriétés anxiolytiques. J Pharmacol (Paris) 7:87–102
Vaughn LK, Quock RM, Meyer RA Jr (1987) Rearing and step climbing behavior of X-linked hypophosphatemic (Hyp) mice. Physiol Behav 40:131–134
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Emmanouil, D.E., Quock, R.M. Effects of benzodiazepine agonist, inverse agonist and antagonist drugs in the mouse staircase test. Psychopharmacology 102, 95–97 (1990). https://doi.org/10.1007/BF02245750
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DOI: https://doi.org/10.1007/BF02245750