Low but Not High Doses of Buspirone Reduce the Anxiogenic Effects of Diazepam Withdrawal

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1991 Jan 1

PMID 1771225

Citations 13

Authors

S E File

N Andrews

Affiliations

Soon will be listed here.

Abstract

After 21 days of treatment with diazepam (2 mg/kg/day IP) rats were tested 24 h after the last injection in the social interaction and elevated plus-maze tests of anxiety. Compared with control-treated rats, they showed significant decreases in social interaction, in the % numbers of entries onto open arms of the plus-maze and in the % of time spent on the open arms, indicating an anxiogenic response on withdrawal from diazepam. Buspirone (200 micrograms/kg SC) significantly increased social interaction in diazepam withdrawn rats and in the plus-maze also this dose significantly reversed the anxiogenic effects of diazepam withdrawal. Buspirone (400 micrograms/kg SC) was without effect in the plus-maze, but buspirone (800 micrograms/kg SC) significantly decreased the % of time spent on open arms in control-treated rats, indicating an anxiogenic effect. In the social interaction test buspirone (800 micrograms/kg SC) was without significant effect. The contrasting effects of the 200 and 800 micrograms/kg doses are discussed in terms of the pre- and post-synaptic actions of buspirone. The findings are consistent with earlier proposals that the increased anxiety during benzodiazepine withdrawal is at least partly caused by an increased release of hippocampal 5-HT.

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References

File S, Hitchcott P . A theory of benzodiazepine dependence that can explain whether flumazenil will enhance or reverse the phenomena. Psychopharmacology (Berl). 1990; 101(4):525-32. DOI: 10.1007/BF02244232. View

Gray J, Green A . GABAB-receptor mediated inhibition of potassium-evoked release of endogenous 5-hydroxytryptamine from mouse frontal cortex. Br J Pharmacol. 1987; 91(3):517-22. PMC: 1853550. DOI: 10.1111/j.1476-5381.1987.tb11244.x. View

Dunn R, Corbett R, Fielding S . Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze. Eur J Pharmacol. 1989; 169(1):1-10. DOI: 10.1016/0014-2999(89)90811-x. View

Pellow S, Johnston A, File S . Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat. J Pharm Pharmacol. 1987; 39(11):917-28. DOI: 10.1111/j.2042-7158.1987.tb03129.x. View

VanderMaelen C, Matheson G, Wilderman R, Patterson L . Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol. 1986; 129(1-2):123-30. DOI: 10.1016/0014-2999(86)90343-2. View

Baldwin H, File S . Flumazenil prevents the development of chlordiazepoxide withdrawal in rats tested in the social interaction test of anxiety. Psychopharmacology (Berl). 1989; 97(3):424-6. DOI: 10.1007/BF00439464. View

File S, Mabbutt P, Andrews N . Diazepam withdrawal responses measured in the social interaction test of anxiety and their reversal by baclofen. Psychopharmacology (Berl). 1991; 104(1):62-6. DOI: 10.1007/BF02244555. View

File S, Zharkovsky A, Gulati K . Effects of baclofen and nitrendipine on ethanol withdrawal responses in the rat. Neuropharmacology. 1991; 30(2):183-90. DOI: 10.1016/0028-3908(91)90202-m. View

Gonsalves S, Gallager D . Persistent reversal of tolerance to anticonvulsant effects and GABAergic subsensitivity by a single exposure to benzodiazepine antagonist during chronic benzodiazepine administration. J Pharmacol Exp Ther. 1988; 244(1):79-83. View

10.

Hitchcott P, File S, Ekwuru M, Neal M . Chronic diazepam treatment in rats causes long-lasting changes in central [3H]-5-hydroxytryptamine and [14C]-gamma-aminobutyric acid release. Br J Pharmacol. 1990; 99(1):11-2. PMC: 1917496. DOI: 10.1111/j.1476-5381.1990.tb14644.x. View

11.

Gonsalves S, Gallager D . Spontaneous and RO 15-1788-induced reversal of subsensitivity to GABA following chronic benzodiazepines. Eur J Pharmacol. 1985; 110(2):163-70. DOI: 10.1016/0014-2999(85)90208-0. View

12.

Moser P, Tricklebank M, Middlemiss D, Mir A, Hibert M, Fozard J . Characterization of MDL 73005EF as a 5-HT1A selective ligand and its effects in animal models of anxiety: comparison with buspirone, 8-OH-DPAT and diazepam. Br J Pharmacol. 1990; 99(2):343-9. PMC: 1917389. DOI: 10.1111/j.1476-5381.1990.tb14706.x. View

13.

File S, Hyde J . A test of anxiety that distinguishes between the actions of benzodiazepines and those of other minor tranquilisers and of stimulants. Pharmacol Biochem Behav. 1979; 11(1):65-9. DOI: 10.1016/0091-3057(79)90298-3. View

14.

Gallager D, Lakoski J, Gonsalves S, Rauch S . Chronic benzodiazepine treatment decreases postsynaptic GABA sensitivity. Nature. 1984; 308(5954):74-7. DOI: 10.1038/308074a0. View

15.

Ashton C, Rawlins M, Tyrer S . A double-blind placebo-controlled study of buspirone in diazepam withdrawal in chronic benzodiazepine users. Br J Psychiatry. 1990; 157:232-8. DOI: 10.1192/bjp.157.2.232. View

16.

Sprouse J, Aghajanian G . Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology. 1988; 27(7):707-15. DOI: 10.1016/0028-3908(88)90079-2. View

17.

Baldwin H, File S . Reversal of increased anxiety during benzodiazepine withdrawal: evidence for an anxiogenic endogenous ligand for the benzodiazepine receptor. Brain Res Bull. 1988; 20(5):603-6. DOI: 10.1016/0361-9230(88)90219-5. View

18.

Kunchandy J, Kulkarni S . Reversal by alpha-2 agonists of diazepam withdrawal hyperactivity in rats. Psychopharmacology (Berl). 1986; 90(2):198-202. DOI: 10.1007/BF00181241. View

19.

Bowery N, Hill D, Hudson A, Doble A, Middlemiss D, Shaw J . (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature. 1980; 283(5742):92-4. DOI: 10.1038/283092a0. View

20.

Costall B, Jones B, Kelly M, Naylor R, Oakley N, Onaivi E . The effects of ondansetron (GR38032F) in rats and mice treated subchronically with diazepam. Pharmacol Biochem Behav. 1989; 34(4):769-78. DOI: 10.1016/0091-3057(89)90273-6. View