Skip to main content
Log in

Effect of aging on anticonflict and CNS depressant activity of diazepam in rats

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

Abstract

Male Fischer 344 rats were examined for an age-dependent sensitivity to the anticonflict and central nervous system (CNS) depressant effects of diazepam. A conflict paradigm was used to measure the ability of single intravenous injections of diazepam to attenuate punishment-induced suppression of behavior and to elicit CNS depression in young, mature, and senescent rats. Senescent rats had the lowest behaviorally active threshold dose. However, diazepam at the behaviorally active threshold dose produced a simultaneous increase in punished and unpunished responding in all three age groups. Punished responding was increased more and over a wider dose range in the young and mature rats than in the senescent rats. Sensitivity to the CNS depressant effects of diazepam was over four times greater in the senescent rats than in the other two age groups. In summary, the results indicate that the behavioral effects of diazepam vary with dosage and age of the rat. The male Fischer 344 rat may be a useful animal model for exploring how diazepam elicits age-related behavioral effects in humans.

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.

Institutional subscriptions

Similar content being viewed by others

References

  • Ayd FJ (1980) Social issues: Misuse and abuse. Psychosomatics 21:21–25

    Google Scholar 

  • Bainbridge JS (1968) The effect of psychotrophic drugs on food-reinforced behaviour and on food consumption. Psychopharmacologia 12:204–212

    Google Scholar 

  • Barrett JE, Valentine JO, Katz JL (1981) Effects of chlordiazepoxide and d-amphetamine on responding of squirrel monkeys maintained under concurrent or second-order schedules of response-produced food or electric shock presentation. J Pharmacol Exp Ther 219:199–206

    Google Scholar 

  • Catania AC, Reynolds GS (1968) A quantitative analysis of the responding maintained by interval schedules of reinforcement by interval schedules of reinforcement. J Exp Anal Behav 11:327–383

    Google Scholar 

  • Cook L, Davidson AB (1973) Effects of behaviorally active drugs in a conflict-punishment procedure in rats. In: Garattini S, Mussini E, Randall IO (eds) The benzodiazepines. Raven, New York, pp 327–345

    Google Scholar 

  • Dantzer R (1977) Behavioral effects of benzodiazepines: A review. Biobehav Rev 1:71–86

    Google Scholar 

  • Dantzer R (1978) Dissociation between suppressive and facilitating effects of aversive stimuli on behavior by benzodiazepines. A review and reinterpretation. Prog Neuro-Psychopharmacol Biol Psychiatry 2:33–40

    Google Scholar 

  • Dardel OV, Mebius C, Mossberg T (1976) Diazepam in emulsion form for intravenous usage. Acta Anaesth Scand 20:221–224

    Google Scholar 

  • Davidson AB, Cook L (1969) Effects of combined treatment with trifluoperazine-HCl and amobarbital on punished behavior in rats. Psychopharmacologia 15:159–168

    Google Scholar 

  • Forster MJ, Retz KC, Popper MD, Lal H (1986) Age-dependent enhancement of diazepam sensitivity is accelerated in New Zealand Black mice. Life Sci 38:1433–1439

    Google Scholar 

  • Geller I (1962) Use of approach avoidance behavior (conflict) for evaluating depressant drugs. In: Nodine JH and Moyer H (ed) Psychosomatic medicine. Lea and Febiger, Philadelphia, pp 267–274

    Google Scholar 

  • Geller I, Seifter J (1960) The effects of meprobamate, barbiturates, l-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492

    Google Scholar 

  • Giles HG, MacLeod SM, Wright JR, Sellers EM (1978) Influence of age and previous use on diazepam dosage required for endoscopy. Can Med Assoc J 118:513–514

    Google Scholar 

  • Howard JL, Pollard GT (1977) The Geller conflict test: A model of anxiety and a screening procedure for anxiolytics. In: Honin I, Usdin E (eds) Animal models in psychiatry and neurology. Pergamon, New York, pp 269–277

    Google Scholar 

  • Iwasaki T, Ezawa K, Iwahara S (1976) Differential effects of chlordiazepoxide on simultaneous and successive brightness discrimination learning in rats. Psychopharmacology 48:75–78

    Google Scholar 

  • Jensen S, Huttel MS, Olesen AS (1981) Venous complications after i.v. administration of diazemuls (Diazepam) and dormicum (Midazolam). Br J Anaesth 53:1083–1085

    Google Scholar 

  • Kleber HD, Gold MS (1978) Use of psychotropic drugs in treatment of methadone maintained narcotic addicts. Ann NY Acad Sci 311:81–96

    Google Scholar 

  • Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR (1975) The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55:347–359

    Google Scholar 

  • Knowler WC, Ukena TE (1973) The effects of chlorpromazine, pentobarbital, chlordiazepoxide and d-amphetamine on rates of licking in the rat. J Pharmacol Exp Ther 184:385–397

    Google Scholar 

  • Maickel RP, Maloney GJ (1973) Effects of various depressant drugs on deprivation-induced water consumption. Neuropharmacology 12:777–782

    Google Scholar 

  • Margules DL, Stein L (1967) Neuroleptics vs. tranquilizers: Evidence from animal behavior studies of mode and site of action. In: Brill H, Cole JD, Deniker P, Hippius H, Bradley PB (ed) Neuropsychopharmacology. Excerpta Medica Foundation, Amsterdam, pp 108–120

    Google Scholar 

  • Mattila MA, Rossi ML, Ruoppi MK, Korhonen M, Larni HM, Kortelainen S (1981) Reduction of venous sequelae of i.v. diazepam with a fat emulsion as solvent. Br J Anaesth 53:1265–1267

    Google Scholar 

  • McSweeney FK, Dougan JD, Higa J, Farmer VA (1986) Behavioral contrast as a function of component duration and baseline rate of reinforcement. Anim Learn Behav 14:173–183

    Google Scholar 

  • Miller RW (1984) Diuretics most prescribed. FDA Consumer 18:6–7

    Google Scholar 

  • Mokler DJ, Rech RH (1985) Mechanisms of the initial treatment phenomenon to diazepam in the rat. Psychopharmacology 87:242–246

    Google Scholar 

  • Pellow S, File SE (1984) Multiple sites of action for anxiogenic drugs: Behavioral, electrophysiological and biochemical correlations. Psychopharmacology 83:305–315

    Google Scholar 

  • Pollard GT, Howard JL (1979) The Geller-Seifter conflict paradigm with incremental shock. Psychopharmacology 62:117–121

    Google Scholar 

  • Pomara N, Stanley B, Black R, Guido J, Stanley M, Greenblatt DJ, Newton RE, Gershon S (1984) Diazepam impairs performance in normal elderly patients. Psychopharmacol Bull 20:137–139

    Google Scholar 

  • Reidenberg MM, Levy M, Warner H, Countinko CB, Schwartz MA, Yui G, Cheripko J (1978) Relationship between diazepam, dose, plasma level, age and central nervous system depression. Clin Pharmacol Ther 23:371–374

    Google Scholar 

  • Rolls BJ, Rolls ET (1982) Thirst. Cambridge University Press, Cambridge

    Google Scholar 

  • Sanger DJ, Blackman DE (1975) The effects of tranquilizing drugs on timing behavior in rats. Psychopharmacologia 44:153–156

    Google Scholar 

  • Schachter S (1971) Some extraordinary facts about obese humans and rats. Am Psychol 26:129–144

    Google Scholar 

  • Sepinwall J, Grodsky FS, Cook L (1978) Conflict behavior in the squirrel monkey: Effects of chlordiazepoxide, diazepam and N-desmethyl-diazepam. J Pharmacol Exp Ther 204:88–102

    Google Scholar 

  • Smith GP (1982) The physiology of the meal. In: Silverston T (ed) Drugs and appetite. Academic Press, London, pp 1–21

    Google Scholar 

  • Solleveld HA, Haseman JK, McConnell EE (1984) Natural history of body weight gain, survival, and neoplasia in the F 344 rat. J Natl Cancer Inst 72:929–940

    Google Scholar 

  • Steel RG, Torrie JH (1980) Principles and procedures of statistics, 2nd Edition. McGraw-Hill, New York, pp 90–188

    Google Scholar 

  • Stitzer ML, Griffiths RR, McLellan T, Graborwski J, Hawthorne JW (1981) Diazepam use among methadone maintenance patients: patterns and dosages. Drug Alcohol Depend 8:189–199

    Google Scholar 

  • Thiebot MH, Soubrie P, Simon P (1985) Is delay of reward mediated by shock-avoidance behavior a critical target for anti-punishment effects of diazepam in rats? Psychopharmacology 87:473–479

    Google Scholar 

  • Treit D (1985) Animal models for the study of anti-anxiety agents: a review. Neurosci Biobehav Rev 9:203–222

    Google Scholar 

  • Uhlenhuth EH, Balter MB, Lipman RS (1978) Minor tranquilizers: clinical correlates of use in an urban population. Arch Gen Psychiatry 35:650–655

    Google Scholar 

  • Wagner JG (1977) Drug bioavailability studies. Hosp Pract 12:119–127

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Komiskey, H.L., Buck, M.A., Mundinger, K.L. et al. Effect of aging on anticonflict and CNS depressant activity of diazepam in rats. Psychopharmacology 93, 443–448 (1987). https://doi.org/10.1007/BF00207233

Download citation

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00207233

Key words

Navigation