Effects of Benzodiazepine Agonist, Inverse Agonist and Antagonist Drugs in the Mouse Staircase Test

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1990 Jan 1

PMID 2118268

Citations 8

Authors

D E Emmanouil

R M Quock

Affiliations

Soon will be listed here.

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

Keane P, Simiand J, Morre M, Biziere K . Tetrazepam: a benzodiazepine which dissociates sedation from other benzodiazepine activities. I. Psychopharmacological profile in rodents. J Pharmacol Exp Ther. 1988; 245(2):692-8. View

Pruhs R, Quock R . Interaction between nitrous oxide and diazepam in the mouse staircase test. Anesth Analg. 1989; 68(4):501-5. View

Quock R, Wojcechowskyj J, Emmanouil D . Comparison of nitrous oxide, morphine and diazepam effects in the mouse staircase test. Psychopharmacology (Berl). 1987; 92(3):324-6. DOI: 10.1007/BF00210838. View

Pruhs R, Kalbfleisch J, Quock R . Combination effects of chloral hydrate and nitrous oxide/oxygen in the mouse staircase test. Anesth Prog. 1988; 35(3):116-20. PMC: 2168025. View

Olsen R . Drug interactions at the GABA receptor-ionophore complex. Annu Rev Pharmacol Toxicol. 1982; 22:245-77. DOI: 10.1146/annurev.pa.22.040182.001333. View

Simiand J, Keane P, Morre M . The staircase test in mice: a simple and efficient procedure for primary screening of anxiolytic agents. Psychopharmacology (Berl). 1984; 84(1):48-53. DOI: 10.1007/BF00432023. View

Lal H, Shearman G, Fielding S, Dunn R, Kruse H, THEURER K . Evidence that GABA mechanisms mediate the anxiolytic action of benzodiazepines: a study with valproic acid. Neuropharmacology. 1980; 19(8):785-9. DOI: 10.1016/0028-3908(80)90071-4. View

Porsolt R, Lenegre A, Avril I, Doumont G . Antagonism by exifone, a new cognitive enhancing agent, of the amnesias induced by four benzodiazepines in mice. Psychopharmacology (Berl). 1988; 95(3):291-7. DOI: 10.1007/BF00181936. View

Steru L, Thierry B, Chermat R, Millet B, Simon P, Porsolt R . Comparing benzodiazepines using the staircase test in mice. Psychopharmacology (Berl). 1987; 92(1):106-9. DOI: 10.1007/BF00215488. View

10.

Pollard G, Howard J . The staircase test: some evidence of nonspecificity for anxiolytics. Psychopharmacology (Berl). 1986; 89(1):14-9. DOI: 10.1007/BF00175182. View

11.

Braestrup C, Nielsen M, Honore T, Jensen L, Petersen E . Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology. 1983; 22(12B):1451-7. DOI: 10.1016/0028-3908(83)90113-2. View

12.

Thiebot M, Soubrie P, Simon P, BOISSIER J . [Dissociation of two components of rat behaviour by psychotropic drugs. Utilization for studying anxiolytic drugs]. Psychopharmacologia. 1973; 31(1):77-90. DOI: 10.1007/BF00429300. View

13.

Shekhar A, HINGTGEN J, Dimicco J . Anxiogenic effects of noreleagnine, a water soluble beta-carboline in rats. Neuropharmacology. 1989; 28(5):539-42. DOI: 10.1016/0028-3908(89)90092-0. View

14.

Belzung C, Misslin R, Vogel E, Dodd R, Chapouthier G . Anxiogenic effects of methyl-beta-carboline-3-carboxylate in a light/dark choice situation. Pharmacol Biochem Behav. 1987; 28(1):29-33. DOI: 10.1016/0091-3057(87)90006-2. View

15.

Vaughn L, Quock R, Meyer Jr R . Rearing and step climbing behavior of X-linked hypophosphatemic (Hyp) mice. Physiol Behav. 1987; 40(1):131-4. DOI: 10.1016/0031-9384(87)90195-8. View

16.

Belzung C, Misslin R, Vogel E . The benzodiazepine receptor inverse agonists beta-CCM and RO 15-3505 both reverse the anxiolytic effects of ethanol in mice. Life Sci. 1988; 42(18):1765-72. DOI: 10.1016/0024-3205(88)90043-4. View

17.

Misslin R, Ropartz P, Mandel P . [Comparison of the effects of di-n-propylacetate and oxazepam on spontaneous and conditioned responses in mice]. C R Acad Hebd Seances Acad Sci D. 1975; 281(16):1175-8. View

18.

Ohmori K, Yamanami S, Shuto K, MARUMO H . Effect of sodium dipropylacetate on conflict behavior in rats. Jpn J Pharmacol. 1980; 30(6):925-7. DOI: 10.1254/jjp.30.925. View