Skip to main content
Log in

The discriminative stimulus properties of zolpidem, a novel imidazopyridine hypnotic

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Zolpidem is a non-benzodiazepine hypnotic drug which displaces benzodiazepines from their binding sites in different brain structures. Previous work has demonstrated several differences between zolpidem and benzodiazepines, including differences between the stimulus properties of zolpidem and chlordiazepoxide. In the present study the discriminative stimulus properties of zolpidem were analysed by training rats to discriminate between this drug and saline. It was found that stimulus control developed readily with 2 mg/kg but not with 1 mg/kg zolpidem. The effect was dose-related, had a short duration of action and was antagonised by Ro 15-1788. Furthermore, stimulus control produced by zolpidem was associated with marked reductions in rates of responding. Injections of chlordiazepoxide, triazolam, lorazepam, zopiclone, CL 218,872 and pentobarbital produced dose-related responding on the zolpidem-associated lever but haloperidol did not. However, in general, the doses of those drugs which produced drug-lever responding also reduced response rates. It is possible that the above mentioned differences between the discriminative stimulus produced by zolpidem in rats and those produced by other sedatives may be due to a selective action of zolpidem on a sub-type of benzodiazepine binding site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arbilla S, Depoortere H, George P, Langer SZ (1985) Pharmacological profile of zolpidem at benzodiazepine receptors and electrocorticogram in rats. Naunyn-Schmiedeberg's Arch Pharmacol 330:248–251

    Google Scholar 

  • Ator NA, Griffiths RR (1983) Lorazepam and pentobarbital drug discrimination in baboons: Cross-drug generalization and interaction with Ro 15–1788. J Pharmacol Exp Ther 226:776–782

    Google Scholar 

  • Ator NA, Griffiths RR (1985) Lorazepam and pentobarbital discrimination: interactions with CGS 8216 and caffeine. Eur J Pharmacol 107:169–181

    Google Scholar 

  • Colpaert FC, Slangen JL (eds) (1982) Drug discrimination: Applications in CNS pharmacology. Elsevier, Amsterdam

    Google Scholar 

  • Colpaert FC, Desmedt LKC, Janssen PAJ (1976) Discriminative stimulus properties of benzodiazepines, barbiturates and pharmacologically related drugs: relation to some intrinsic and anticonvulsant effects. Eur J Pharmacol 37:113–123

    Google Scholar 

  • Dantzer R, Perio A (1982) Behavioural evidence for partial agonist properties of Ro 15–1788, a benzodiazepine receptor antagonist. Eur J Pharmacol 81:655–658

    Google Scholar 

  • Depoortere H, Zivkovic B, Lloyd KG, Sanger DJ, Perrault G, Langer SZ, Bartholini G (1986) Zolpidem, a novel non-benzodiazepine hypnotic. I — Neuropharmacological and behavioral effects. J Pharmacol Exp Ther (in press)

  • Garcha HS, Rose IC, Stolerman IP (1985) Midazolam cue in rats: Generalization tests with anxiolytic and other drugs. Psychopharmacology 87:233–237

    Google Scholar 

  • Haug T (1983) Neuropharmacological specificity of the diazepam stimulus complex: effects of agonists and antagonists. Eur J Pharmacol 93:221–227

    Google Scholar 

  • Haug T, Gotestam KG (1982) The diazepam stimulus complex: specificity in a rat model. Eur J Pharmacol 80:225–230

    Google Scholar 

  • Herling S, Shannon HE (1982) Ro 15–1788 antagonizes the discriminative stimulus effects of diazepam in rats but not similar effects of pentobarbital. Life Sci 31:2105–2112

    Google Scholar 

  • Hunkeler W, Mohler H, Pieri L, Polc L, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516

    Google Scholar 

  • Johansson JO, Jarbe TUC (1975) Diazepam as a discriminative cue: its antagonism by bemegride. Eur J Pharmacol 30:372–375

    Google Scholar 

  • Lippa AS, Coupet J, Greenblatt EN, Klepner CA, Beer B (1979) A synthetic non-benzodiazepine ligand for benzodiazepine receptors: A probe for investigating neuronal substrates of anxiety. Pharmacol Biochem Behav 11:99–106

    Google Scholar 

  • Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–113

    Google Scholar 

  • McElroy JF, Feldman RS (1982) Generalization between benzodiazepine-and triazolopyridazine-elicited discriminative cues. Pharmacol Biochem Behav 17:709–713

    Google Scholar 

  • Nicholson AN, Pascoe DA (1986) Hypnotic activity of an imidazopyridine (zolpidem). Br J Clin Pharmacol 21:205–211

    Google Scholar 

  • Overton DA (1966) State-dependent learning produced by depressant and atropine-like drugs. Psychopharmacologia 10:6–31

    Google Scholar 

  • Overton DA (1976) Discriminable effects of benzodiazepines. Psychopharmacol Commun 2:339–343

    Google Scholar 

  • Sanger DJ, Joly D, Zivkovic B (1985) Behavioral effects of non-benzodiazepine anxiolytic drugs: A comparison of CGS 9896 and zopiclone with chlordiazepoxide. J Pharmacol Exp Ther 232:831–837

    Google Scholar 

  • Schechter MD (1984) Specific antagonism of the behavioral effects of chlordiazepoxide and pentobarbital in the rat. Prog. Neuro-Psychopharmacol Biol Psychiatr 8:359–364

    Google Scholar 

  • Shannon HE (1984) Stimulus control by diazepam of behavior maintained under fixed-ratio stimulus-shock termination schedules in rats. Pharmacol Biochem Behav 20:715–720

    Google Scholar 

  • Shannon HE, Davis SL (1984) CGS 8216 non competitively antagonizes the discriminative effects of diazepam in rats. Life Sci 34:2589–2596

    Google Scholar 

  • Shannon HE, Herling S (1983) Discriminative stimulus effects of diazepam in rats: Evidence for a maximal effect. J Pharmacol Exp Ther 227:160–166

    Google Scholar 

  • Winter JC (1978) Drug-induced stimulus control, In: Blackman DE, Sanger DJ (eds) Contemporary research in behavioral pharmacology, Plenum, New York

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Offprint requests to: D.J. Sanger

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanger, D.J., Zivkovic, B. The discriminative stimulus properties of zolpidem, a novel imidazopyridine hypnotic. Psychopharmacology 89, 317–322 (1986). https://doi.org/10.1007/BF00174367

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00174367

Key words

Navigation