Abstract
Acquisition of passive avoidance following aversive conditioning to a dark compartment was measured in mice under the influence of one of seven bezodiazepines, the GABA-mimetic drug progabide or PK 9084, a nonbenzodiazepine ligand on benzodiazepine receptors.
The drugs were administered prior to the training trial and retention was measured in the absence of the drug 24 h later. Oral administration (dose in mg/kg in parentheses) of flunitrazepam (0.1), lorazepam (1.0), nitrazepam (3.0), diazepam (10), flurazepam (10) and chlordiazepoxide (30), all prevented retention whereas progabide (100–800) and PPK 9084 (10–100) were ineffective. In comparison to effects on motor capacity none of the benzodiazepines was outstanding in its acquisition interfering effects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ahtee L, Shillito E (1970) The effects of benzodiazepines and atropine on exploratory behaviour and motor activity of mice. Br J Pharmacol 40:361–371
Baird ES, Hailey DM (1972) Delayed recovery from a sedative: correlation of the plasma levels of diazepam with clinical effects after oral and intravneous administration. Br J Anaesth. 44:803–808
Biagi GL, Barbaro AM, Guerra MC, Babbini M, Gaiardi M, Bartoletti M, Borea PA (1980) RM values and structure-activity relationships of benzodiazepines. J Med Chem 23:193–201
Bovier P, Broekkamp CL, Lloyd KG (1982) Enhancing gabaergic transmission reverses the aversive state in rats induced by electrical stimulation of the periaqueductal grey region. Brain Res 248:313–320
Bowery NG, Hill DR, Hudson AL (1982) Evidence that SL 75102 is an agonist at GABA B as well as GABA A receptors. Neuropharmacology 21:391–395
Braestrup C, Albrechtsen R, Squires RF (1977) High densities of benzodiazepine receptors in human cortical areas. Nature 269:702–704
Brandt AL, Oakes FD (1965) Pre-anesthesia medication: double blind study of a new drug, diazepam. Anesth Analg Curr Res 44:125–129
Brown SS, Dundee JW (1968) Clinical studies of induction agents. XXV. Diazepam. Br J Anaesth 40:108–112
Costa E (1980) Benzodiazepines and transmitters. Arzneim Forsch 30:858–864
Edwards JG (1981) Adverse effects of antianxiety drugs. Drugs 22:495–514
Gee KW, Brinton RE, Yamamura HI (1983a) PK 8165 and PK 9084, two quinoline derivatives with anxiolytic properties, antagonize the anticonvulsant effects of diazepam. Brain Res 264:168–172
Gee KW, Ehlert FJ, Yamamura HI (1983b) Differential effect of γ-aminobutyric acid on benzodiazepine receptor subtypes labelled by [3H] propyl β-carboline-3-carboxylate in rat brain. J Pharmacol Exp Ther 225:132–137
Grecksch G, Wetzel W, Matthies H (1978) Effect of n-dipropylacetate on the consolidation of brightness discrimination. Pharmacol Biochem Behav 9:269–271
Harry FVA, Richards DJ (1971) Lorazepam: a study in psychomotor depression. Br J Clin Pract 26:371–373
Heisterkamp DV, Cohen PJ (1975) The effect of intravenous premedication with lorazepam (Ativan), pentobarbitone or diazepam on recall. Br J Anaesth 47:79–81
Hendler N, Cimini C, Ma T, Long D (1980) A comparison of cognitive impairment due to benzodiazepines and to narcotics. Am J Psychiatry 137:828–830
Ishikawa K, Saito S (1978) Effect of intraventricular γ-aminobutyric acid (GABA) on discrimination learning in rats. Psychopharmacology 56:127–132
Jaattela A, Mannisto P, Paatero H, Tuomisto J (1971) The effects of diazepam or diphenhydramine on healthy human subjects. Psychopharmacologia 21:202–211
Jensen RA, Martinez JL, Vasquez BJ, McGaugh JL (1979) Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice. Psychopharmacology 64:125–126
Jobert A, Thiébot MH, Soubrié P (1979) A comparative study of the effects of muscimol and diazepam on the recall of noxious events. Experientia 35:239–240
Kaplan SA (1980) Pharmacokinetics of the benzodiazepines. In: Priest RG, Filhs UV, Amrein R, Skreta M (eds) Benzodiazepines today and tomorrow. MTP, Lancaster, pp 47–60
Katz RJ, Liebler L (1978) GABA involvement in memory consolidation: evidence from posttrial amino-oxyacetic acid. Psychopharmacology 56:191–193
Kleinknecht RA, Donaldson DA (1975) A review of the effects of diazepam on cognitive and psychomotor performance. J Nerv Ment Dis 161:399–411
Komiskey HL, Cook TM, Lin C-F, Hayton WL (1981) Impairment of learning or memory in the mature and old rat by diazepam. Psychopharmacology 73:304–305
Korttila K, Linnoila M (1974) Skills related to driving after intravenous diazepam, flunitrazepam or droperidol. Br J Anaesth 46:961–969
Le Fur G, Mizoule J, Burgevin MC, Ferris O, Heaulme M, Gauthier A, Gueremy C, Uzan A (1981) Multiple benzodiazepine receptors: evidence of a dissociation between anticonflict and anticonvulsant properties by PK 8165 and PK 9084 (two quinoline derivatives). Life Sci 28:1439–1448
Lloyd KG, Arbilla S, Beaumont K, Briley M, De Montis G, Scatton B, Langer SZ, Bartholini G (1982) Gamma-aminobutyric acid (GABA) receptor stimulation. II. Specificity of progabide (SL 76002) and SL 75102 for the GABA receptor. J Pharmacol Exp Ther 220:672–677
Mattila MAK, Säilä K, Kokko T, Kärkkäinen T (1979) Comparison of diazepam and flunitrazepam as adjuncts to general anaesthesia in preventing arousal following surgical stimuli. Br J Anaesth 51:329–337
Mattila MAK, Larni HM (1980) Flunitrazepam: a review of its pharmacological properties and therapeutic use. Drugs 20:353–374
Misslin R, Ropartz Ph, Mandel P (1975) The effects of n-dipropylacetate on the acquisition of conditioned behaviour with negative reinforcement in mice. Psychopharmacologia 44:263–265
Patel J, Ciotalo VB, Jorio LC (1979) Benzodiazepine blockade of passive-avoidance task in mice: a state-dependent phenomenon. Psychopharmacology 61:25–28
Petersen RC, Ghoneim MM (1980) Diazepam and human memory: influence on acquisition, retrieval, and state-dependent learning. Prog Neuro-Psychopharmacol 4:81–89
Randall LD, Shallek W, Sternbach LH, Ning RY (1974) Chemistry and pharmacology of the 1,4-benzodiazepines. In: Gordon M (ed) Psychoparmacological agents, medicinal chemistry, a series of monographs, vol 4-III. Academic Press, New York, pp 175–281
Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD (1978) Impaired absorption of desmethyldiazepam from chlorazepate by magnesium aluminium hydroxide. Clin Pharmacol Ther 24:308–315
Siegel S (1956) Nonparametric statistics for the behavioral sciences. McGraw-Hill, London
Soubrié P, Simon P, Boissier JR (1976) An amnesic effect of benzodiazepines in rats. Experientia 32:359–360
Soubrié P, Simon P, Boissier JR (1976) Conditioned suppression: dissociation of learning in baclofen treated rats. Experientia 32:1323–1324
Squires RF, Braestrup C (1977) Benzodiazepine receptors in rat brain. Nature 266:732–734
Wilson J, Ellis FR (1973) Oral premedication with lorazepam (activam): a comparison with heptabarbitone (Medomin) and diazepam (valium). Br J Anaesth 45:738–744
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Broekkamp, C.L., Le Pichon, M. & Lloyd, K.G. The comparative effects of benzodiazepines, progabide and PK 9084 on acquisition of passive avoidance in mice. Psychopharmacology 83, 122–125 (1984). https://doi.org/10.1007/BF00427435
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427435