Abstract
The effects were compared of three 2' chloro-phenyl-benzodiazepines (triazolam, clonazepam and lorazepam) and three corresponding 2' deschloro-phenylderivatives (alprazolam, nitrazepam and oxazepam, respectively) on the incidence of six ethological elements in both timid and aggressive singly-housed male mice, treated with drugs in paired interactions with untreated non-aggressive males. Alprazolam and oxazepam reduced defensive upright postures and escapes at doses which did not reduce rearing and actually increased walking, while their chlorinated counterparts (triazolam and lorazepam, respectively) decreased incidence of defenses and escapes mostly at doses decreasing locomotor acts involving a similar movement (rears and walks, respectively). Alprazolam and oxazepam also reduced attacks at doses not reducing rears, in contrast to triazolam and lorazepam which reduced attacks only at doses suppressing rearing. Nitrazepam stimulated sniffing partners much more than its chlorinated counterpart clonazepam. The 2′ deschloro-phenyl-benzodiazepines were more potent in reducing defensive-escape activities than attacks or locomotion. Yet, none of the benzodiazepines tested produced a complete inhibition of timid defensive-escape behavior at non-sedative doses. The present study suggests that 2′ deschloro-phenyl-benzodiazepines are less “sedative” with respect to their “anxiolytic” activity.
Similar content being viewed by others
References
Arendt RM, Greenblatt DJ, Liebisch DC, Luu MD, Paul SM (1987) Determinants of benzodiazepine brain uptake: lipophilicity versus binding affinity. Psychopharmacology 93:72–77
Blanchard DC, Hori K, Rodgers RJ, Hendrie CA, Blanchard RJ (1989) Attenuation of defensive threat and attack in wild rats (Rattus rattus) by benzodiazepines. Psychopharmacology 97:392–401
Bond A, Lader M (1988) Differential effects of oxazepam and lorazepam on aggressive responding. Psychopharmacology 95:369–373
Braestrup C, Squires RF (1978) Brain specific benzodiazepine receptors. Br J Psychiatry 133:249–260
Connor JL (1975) Genetic mechanisms controlling the domestication of a wild house mouse population (Mus musculus L.). J Comp Physiol Psychol 89: 118–130
Crowcroft P (1966) Mice all over. Foulis, London
Curran HV, Schiwy W, Lader M (1987) Differential amnestic properties of benzodiazepines: a dose-response comparison of two drugs with similar elimination half-lives. Psychopharmacology 92:358–364
D'Amato FR, Castellano C (1988) Behavioral effects of morphine in timid isolated and non-aggressive grouped mice. Psychopharmacology 96: S12
Dantzer R (1977) Behavioral effects of benzodiazepines: a review. Biobehav Rev 1:71–86
Dixon AK (1982) Ethopharmacology: a new way to analyse drug effects on behavior. Triangle 21:95–105
Dixon AK, Kaesermann HP (1987) Ethopharmacology of flight behavior. In: Olivier B, Mos J, Brain PF (eds) Ethopharmacology of agonistic behavior in animals and humans. Martinus Nijhoff, Dordrecht, pp 46–79
Donat P, Krsiak M (1985) Pheromone stimulates not only aggressive but also defensive-escape behaviour in mice. Activ Nerv Supp (Praha) 27:153–154
File S (1980) The use of social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods 2:219–238
Grant EC, Mackintosh JH (1963) A comparison of the social postures of some common laboratory rodents. Behavior 21:246–259
Greenblatt DJ, Shader RI (1987) Pharmacokinetics of antianxiety agents. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 1377–1386
Haefely W, Kyburz E, Gerecke M, Mohler H (1985) Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationships of their agonists and antagonists. In: Testa B (ed) Advances in drug research, vol 14. Academic Press, London, pp 165–322
Iversen SD (1985) Where in the central nervous system do benzodiazepines act? In: Iversen SD (ed) Psychopharmacology: recent advances and future prospects. British Association for Psychopharmacology Monograph, vol 6. Oxford University Press, Oxford, pp 75–88
Krsiak M (1975) Timid singly-housed mice: their value in prediction of psychotropic activity of drugs. Br J Pharmacol 55:141–150
Krsiak M (1979) Effects of drugs on behavior of aggressive mice. Br J Pharmacol 65:525–533
Krsiak M (1980) The study of neuropsychotropic effects of drugs by ethological analysis of behavior (DSc Thesis, in Czech). Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague
Krsiak M, Sulcova A, Donat P, Tomasikova Z, Dlohozkova N, Kosar E, Masek K (1984) Can social and agonistic interactions be used to detect anxiolytic activity of drugs? In: Miczek KA, Kruk MR, Olivier B (eds) Ethopharmacological aggression research. Liss, New York, pp 93–114
Lader M (1980) The present status of the benzodiazepines in psychiatry and medicine. Arzneim Forsch/Drug Res 30:910–913
Miczek KA (1987) The psychopharmacology of aggression. In: Iversen JL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 19. Plenum Press, New York, pp 183–328
Miczek KA, Krsiak M (1981) Pharmacological analysis of attack and flight. In: Brain PF, Benton D (eds) A multidisciplinary approaches to aggression research. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 341–354
Muller WE, Stillbauer AE (1983) Benzodiazepine hypnotics: time course and potency of benzodiazepine receptor occupation after oral application. Pharmacol Biochem Behav 18:545–549
Olivier B, van Aken H, Jaarsma I, van Oorschot R, Zethof T, Bradford D (1984) Behavioral effects of psychoactive drugs on agonistic behavior of male territorial rats (resident — intruder model). In: Miczek KA, Kruk MR, Olivier B (eds) Ethopharmacological aggression research. Liss, New York, pp 137–156
Poshivalov VP (1978) Ethological analysis of the action exerted by medazepam and diazepam on the zoosocial behavior of isolated mice (in Russian). Farmakologiya i Toksikologiya 41:263–265
Robitaille JA, Bovet J (1976) Field observations on the social behavior of the Norway rat,Rattus norvegicus (Berkenhout). Biol Behav 1:289–308
Rodgers RJ, Waters AJ (1985) Benzodiazepines and their antagonists: a pharmacoethological analysis with particular reference to effects on “aggression”. Neurosci Biobehav Rev 9:21–35
Rudzik AD, Hester JB, Tang AH, Straw RN, Friis W (1973) Triazolobenzodiazepines, a new class of central nervous system depressant compounds. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven Press, New York, pp 285–297
Silverman AP (1965) Ethological and statistical analysis of drug effects on the social behavior of laboratory rats. Br J Pharmacol Chemother 24:579–590
Sternbach LH (1973) Chemistry of 1,4-benzodiazepines and some aspects of the structure-activity relationship. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven Press, New York, pp 1–26
Steru L, Chermat R, Millet B, Mico JA, Simon P (1986) Comparative study in mice of ten 1,4-benzodiazepines and of clobazam: anticonvulsant, anxiolytic, sedative, and myorelaxant effects. Epilepsia [Suppl 1]:27 S14-S17
Subhan Z, Harrison C, Hindmarch I (1986) Alprazolam and lorazepam: single and multiple-dose effects on psychomotor skills and sleep. Eur J Clin Pharmacol 29:709–712
Sulcova A, Krsiak M (1989) Differences among nine 1,4-benzodiazepines: an ethopharmacological evaluation in mice. Psychopharmacology 97:157–159
Wood PL, Loo P, Braunwalder A, Yokoyama N, Cheney DL (1984) In vitro characterization of benzodiazepine receptor agonists, antagonists, inverse agonists and agonist/antagonists. J Pharmacol Exp Ther 231:572–576
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Krsiak, M., Sulcova, A. Differential effects of six structurally related benzodiazepines on some ethological measures of timidity, aggression and locomotion in mice. Psychopharmacology 101, 396–402 (1990). https://doi.org/10.1007/BF02244060
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244060