Abstract
Opposite effects were observed of ethanol on the behaviour of mice in the two chambered light/dark test. At a low dose, it had anxiogenic effects, while it produced anxiolytic effects at a higher dose. Selective antagonistic actions of RO 15-4513 against the behavioural effects of ethanol have been reported by others without intrinsic actions. In contrast, we found intrinsic depressive properties of RO 15-4513. This drug reduced locomotion in a running wheel test. We suggest that RO 15-4513 reversed certain effects of ethanol in an additive, rather than interactive, manner. In addition, RO 15-4513 did not block the sedation produced by a high dose of ethanol. Since RO 15-4513 revealed proconvulsant properties, it is proposed that the depressive effects of this drug could be related to its proconvulsive activity.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Belzung C, Misslin R, Vogel E, Dodd RH, Chapouthier G (1987) Anxiogenic effects of methyl-β-carboline-3-carboxylate in a light/dark choice situation. Pharmacol Biochem Behav 28:29–34
Blumstein L, Crawley JN (1983) Further characterization of a simple automated exploratory model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 18:37–40
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] 18:30
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
Crawley JN (1981) Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines. Pharmacol Biochem Behav 15:695–699
Crawley JN, Goodwin FK (1980) Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 13:167–170
Koob GF, Braestrup C, Thatcher Britton K (1986) The effects of FG 7142 and RO 15–1788 on the release of punished responding produced by chlordiazepoxide and ethanol in the rats. Psychopharmacology 90:173–178
Massotti M (1985) Electroencephalographic investigations in rabbits of drugs acting at GABA-benzodiazepine-barbiturate/picrotoxin receptor complex. Pharmacol Biochem Behav 23:661–670
Misslin R, Cigrang M, Ropartz P, Mandel P (1984) Effects de l'alcohol éthylique sur les conduites de la souris confrontée avec des situations nouvelles. Biol Behav 9:257–269
Möhler H, Sieghart W, Richards JG, Hunkeler W (1984) Photoaffinity labeling of benzodiazepine receptors with a partial inverse agonist. Eur J Pharmacol 102:191–192
Petersen EN, Paschelke G, Kehr W, Nielsen M, Braestrup C (1982) Does the reversal of the anti-conflict effect of phenobarbital by β-CCE and FG 7142 indicate benzodiazepine receptor-mediated anxiogenic properties? Eur J Pharmacol 82:217–221
Pohorecky LA (1981) The interaction of alcohol and stress. A review. Neurosci Biobehav Rev 5:209–229
Polc P (1985) Interactions of partial inverse benzodiazepine agonists RO 15-4513 and FG 7142 with ethanol in rats and cats. Br J Pharmacol 86:465P
Prado de Carvalho L, Grecksch G, Chapouthier G, Rossier J (1983) Anxiogenic and non-anxiogenic benzodiazepine antagonists. Nature 301:64–66
Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM (1986) A selective imidazodiazepine antagonist of ethanol in the rat. Science 234:1243–1247
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Misslin, R., Belzung, C. & Vogel, E. Interaction of RO 15-4513 and ethanol on the behaviour of mice: antagonistic or additive effects?. Psychopharmacology 94, 392–396 (1988). https://doi.org/10.1007/BF00174695
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00174695