Psychopharmacology

, Volume 93, Issue 4, pp 443–448 | Cite as

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

  • H. L. Komiskey
  • M. A. Buck
  • K. L. Mundinger
  • F. K. McSweeney
  • V. A. Farmer-Dougan
  • J. D. Dougan
Original Investigations
Revised:

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.

Key words

Diazepam Conflict paradigm Age-dependent sensitivity Central nervous system depression 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ayd FJ (1980) Social issues: Misuse and abuse. Psychosomatics 21:21–25Google Scholar
  2. Bainbridge JS (1968) The effect of psychotrophic drugs on food-reinforced behaviour and on food consumption. Psychopharmacologia 12:204–212Google Scholar
  3. 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 219:199–206Google Scholar
  4. 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 11:327–383Google Scholar
  5. 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 327–345Google Scholar
  6. Dantzer R (1977) Behavioral effects of benzodiazepines: A review. Biobehav Rev 1:71–86Google Scholar
  7. 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 2:33–40Google Scholar
  8. Dardel OV, Mebius C, Mossberg T (1976) Diazepam in emulsion form for intravenous usage. Acta Anaesth Scand 20:221–224Google Scholar
  9. Davidson AB, Cook L (1969) Effects of combined treatment with trifluoperazine-HCl and amobarbital on punished behavior in rats. Psychopharmacologia 15:159–168Google Scholar
  10. Forster MJ, Retz KC, Popper MD, Lal H (1986) Age-dependent enhancement of diazepam sensitivity is accelerated in New Zealand Black mice. Life Sci 38:1433–1439Google Scholar
  11. 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 267–274Google Scholar
  12. Geller I, Seifter J (1960) The effects of meprobamate, barbiturates, l-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492Google Scholar
  13. 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 118:513–514Google Scholar
  14. 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 269–277Google Scholar
  15. Iwasaki T, Ezawa K, Iwahara S (1976) Differential effects of chlordiazepoxide on simultaneous and successive brightness discrimination learning in rats. Psychopharmacology 48:75–78Google Scholar
  16. Jensen S, Huttel MS, Olesen AS (1981) Venous complications after i.v. administration of diazemuls (Diazepam) and dormicum (Midazolam). Br J Anaesth 53:1083–1085Google Scholar
  17. Kleber HD, Gold MS (1978) Use of psychotropic drugs in treatment of methadone maintained narcotic addicts. Ann NY Acad Sci 311:81–96Google Scholar
  18. 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 55:347–359Google Scholar
  19. 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 184:385–397Google Scholar
  20. Maickel RP, Maloney GJ (1973) Effects of various depressant drugs on deprivation-induced water consumption. Neuropharmacology 12:777–782Google Scholar
  21. 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 108–120Google Scholar
  22. 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 53:1265–1267Google Scholar
  23. 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 14:173–183Google Scholar
  24. Miller RW (1984) Diuretics most prescribed. FDA Consumer 18:6–7Google Scholar
  25. Mokler DJ, Rech RH (1985) Mechanisms of the initial treatment phenomenon to diazepam in the rat. Psychopharmacology 87:242–246Google Scholar
  26. Pellow S, File SE (1984) Multiple sites of action for anxiogenic drugs: Behavioral, electrophysiological and biochemical correlations. Psychopharmacology 83:305–315Google Scholar
  27. Pollard GT, Howard JL (1979) The Geller-Seifter conflict paradigm with incremental shock. Psychopharmacology 62:117–121Google Scholar
  28. 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 20:137–139Google Scholar
  29. 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 23:371–374Google Scholar
  30. Rolls BJ, Rolls ET (1982) Thirst. Cambridge University Press, CambridgeGoogle Scholar
  31. Sanger DJ, Blackman DE (1975) The effects of tranquilizing drugs on timing behavior in rats. Psychopharmacologia 44:153–156Google Scholar
  32. Schachter S (1971) Some extraordinary facts about obese humans and rats. Am Psychol 26:129–144Google Scholar
  33. 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 204:88–102Google Scholar
  34. Smith GP (1982) The physiology of the meal. In: Silverston T (ed) Drugs and appetite. Academic Press, London, pp 1–21Google Scholar
  35. 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 72:929–940Google Scholar
  36. Steel RG, Torrie JH (1980) Principles and procedures of statistics, 2nd Edition. McGraw-Hill, New York, pp 90–188Google Scholar
  37. Stitzer ML, Griffiths RR, McLellan T, Graborwski J, Hawthorne JW (1981) Diazepam use among methadone maintenance patients: patterns and dosages. Drug Alcohol Depend 8:189–199Google Scholar
  38. 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 87:473–479Google Scholar
  39. Treit D (1985) Animal models for the study of anti-anxiety agents: a review. Neurosci Biobehav Rev 9:203–222Google Scholar
  40. Uhlenhuth EH, Balter MB, Lipman RS (1978) Minor tranquilizers: clinical correlates of use in an urban population. Arch Gen Psychiatry 35:650–655Google Scholar
  41. Wagner JG (1977) Drug bioavailability studies. Hosp Pract 12:119–127Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • H. L. Komiskey
    • 1
  • M. A. Buck
    • 2
  • K. L. Mundinger
    • 1
  • F. K. McSweeney
    • 2
  • V. A. Farmer-Dougan
    • 3
  • J. D. Dougan
    • 3
  1. 1.Department of Biomedical SciencesUniversity of Illinois College of Medicine at RockfordRockfordUSA
  2. 2.Department of PsychologyWashington State UniversityPullmanUSA
  3. 3.Department of PsychologyIndiana UniversityBloomingtonUSA

Personalised recommendations