Abstract
After 7 day's gradual introduction of ethanol, rats were maintained for a further 4 weeks on a liquid diet containing 10% ethanol (mean daily dose 11.8±0.2 g/kg/day). Control-treated rats received liquid diet alone. Pairs of rats were tested in the social interaction test of anxiety 8 h after withdrawal. Withdrawal from ethanol significantly reduced the time spent in social interaction compared with controls, indicating an anxiogenic withdrawal response. Nitrendipine (50 mg/kg) had no effect on, whereas flumazenil (4 mg/kg) significantly reversed, this withdrawal response. This reversal appeared to be long-lasting as there was still no evidence of increased anxiety when rats were again withdrawn after 3 more days of ethanol diet.
Similar content being viewed by others
References
Adinoff B, Majchrowicz E, Martin PR, Linnoila M (1986) The benzodiazepine antagonist Ro 15-1788 does not antagonize the ethanol withdrawal syndrome. Biol Psychiatry 21:643–649
Baldwin HA, File SE (1988) Reversal of increased anxiety during benzodiazepine withdrawal: evidence for an anxiogenic endogenous ligand for the benzodiazepine receptor. Brain Res Bull 20:603–606
Baldwin HA, File SE (1989) Flumazenil prevents the development of chlordiazepoxide withdrawal in rats tested in the social interaction test of anxiety. Psychopharmacology (in press)
Cohen G (1976) Alkaloid products in the metabolism of alcohol and biogenic amines. Biochem Pharmacol 25:1123–1128
Costall B, Kelly ME, Naylor RJ (1988) The anxiolytic and anxiogenic actions of ethanol in a mouse model. J Pharm Pharmacol 40:197–202
File SE, Hyde JRG, Pool M (1976) Effects of ethanol and chlordiazepoxide on social interaction in rats. Br J Pharmacol 58:465P
File SE (1980) The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods 2:219–238
File SE, Pellow S (1986) Intrinsic actions of the benzodiazepine receptor antagonist RO 15-1788. Psychopharmacology 88:1–11
Gallager DW, Heninger K, Heninger G (1986) Periodic benzodiazepine antagonist administration prevents benzodiazepine withdrawal in primates. Eur J Pharmacol 132:31–38
Lamb RJ, Griffiths RR (1985) Effects of repeated Ro 15-1788 administration in benzodiazepine-dependent baboons. Eur J Pharmacol 110:257–261
Lister RG, Greenblatt DJ, Abernethy DR, File SE (1984) Pharmacokinetic studies on Ro 15-1788, a benzodiazepine receptor ligand, in the brain of the rat. Brain Res 290:183–186
Little HJ, Taylor SC, Nutt DJ, Cowen PJ (1985) The benzodiazepine antagonist, RO 15-1788 does not decrease ethanol withdrawal convulsions in rats. Eur J Pharmacol 107:375–377
Little HJ, Dolin SJ, Halsey MJ (1986) Calcium channel antagonists decrease the ethanol withdrawal syndrome. Life Sci 39:2059–2065
Nutt DJ, Costello MJ (1988) Rapid induction of lorazepam dependence and reversal with flumazenil. Life Sci 43:1045–1054
Pellow S, File SE (1984) Multiple sites of action for anxiogenic drugs, behavioural, electrophysiological and biochemical correlations. Psychopharmacology 83:304–315
Suzdak PD, Glowa JR, Crawley JN, Schwartz RD, Skolnick P, Paul SM (1986) A selective imidazobenzodiazepine antagonist of ethanol in the rat. Science 234:1243–1247
Ticku MK, Burch TP, Davis WC (1983) The interactions of ethanol with the benzodiazepine-GABA receptor-ionophore complex. Pharmacol Biochem Behav 18:15–18
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
File, S.E., Baldwin, H.A. & Hitchcott, P.K. Flumazenil but not nitrendipine reverses the increased anxiety during ethanol withdrawal in the rat. Psychopharmacology 98, 262–264 (1989). https://doi.org/10.1007/BF00444702
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00444702