Abstract
Some characteristics of the discriminative stimulus (cue) effects of midazolam, a short-acting benzodiazepine, have been determined in rats. A standard two-bar operant conditioning procedure with food reinforcers delivered on a tandem schedule was used. The 0.4 mg/kg dose of midazolam used for training was well discriminated, typically yielding at least 95% correct responding. Other benzodiazepines increased the percentage of drug-appropriate responding in a dose-related manner and were generalized at doses which had little effect on the overall rate of responding. Doses of pentobarbitone which greatly reduced the overall rate of responding were also generalized with midazolam. Amphetamine, oxotremorine, picrotoxin, morphine, nicotine, quipazine and Ro 15-1788 were not generalized, even at doses which severely suppressed overall response rates. The midazolam cue possesses a considerable degree of specificity and provides a potentially useful assay for drug action at the benzodiazepine receptor complex.
Similar content being viewed by others
References
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
Barry H III, Krimmer EC (1979) Differential stimulus attributes of chlordiazepoxide and pentobarbital. Neuropharmacology 18:991–998
Colpaert FC, Slangen JL (eds) (1982) Drug discrimination: Applications in CNS pharmacology. Elsevier, Amsterdam
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
Colpaert FC, Niemegeers CJE, Janssen PAJ (1980) Factors regulating drug cue sensitivity: the effect of training dose in fentanylsaline discrimination. Neuropharmacology 19:705–713
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
Haug T, Gotestam KG (1982) The diazepam stimulus complex: specificity in a rat model. Eur J Pharmacol 80:225–230
Hendry JS, Balster RL, Rosecrans JA (1983) Discriminative stimulus properties of buspirone compared to central nervous system stimulants in rats. Pharmacol Biochem Behav 19:97–101
Hunkeler W, Mohler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516
Johnasson JO, Jarbe TUC (1975) Diazepam as a discriminative cue: its antagonism by bemegride. Eur J Pharmacol 30:372–375
Mohler H, Richards JG (1983) Receptors for anxiolytic drugs. In: Malick JB, Enna SJ, Yamamura HI (eds) Anxiolytics: neurochemical, behavioral, and clinical perspectives. Raven, New York, pp 15–40
Overton DA (1966) State-dependent learning produced by depressant and atropine-like drugs. Psychopharmacologia 10:6–31
Overton DA (1976) Discriminable effects of benzodiazepines. Psychopharmacol Commun 2:339–343
Paul SM, Marangos PJ, Skolnick P (1981) the benzodiazepine — GABA-chloride ionophore receptor complex: common site of minor tranquillizer action. Biol Psychiatry 16:213–229
Pieri L, Schaffner R, Scherschlicht R, Pole P, Sepinwall J, Davidson A, Mohler H, Cumin R, Da Prada M, Burkard WP, Keller HH, Muller RKM, Gerold M, Pieri M, Cook L, Haefely W (1981) Pharmacology of midazolam. Drug Res 31:2180–2201
Pratt JA, Stolerman IP, Garcha HS, Giardini V, Feyerabend C (1983) Discriminative stimulus properties of nicotine: further evidence for mediation at a cholinergic receptor. Psychopharmacology 81:54–60
Rose IC, Stolerman IP (1984) Discriminative stimulus effects of midazolam in rats. Br J Pharmacol 82:239P
Shannon HE, Herling S (1983) Discriminative stimulus effects of diazepam in rats: evidence for a maximal effect. J Pharmacol Exp Ther 227:160–166
Stolerman IP, D'Mello GD (1981) Role of training conditions in discrimination of central nervous system stimulants by rats. Psychopharmacology 73:295–303
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Garcha, H.S., Rose, I.C. & Stolerman, I.P. Midazolam cue in rats: Generalization tests with anxiolytic and other drugs. Psychopharmacology 87, 233–237 (1985). https://doi.org/10.1007/BF00431814
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00431814