, Volume 83, Issue 1, pp 79–81 | Cite as

Effect of diazepam on plasma corticosterone levels

  • Danka Peričić
  • Nela Lakić
  • Hari Manew
Original Investigations


In light of the numerous but rather conflicting reports on the action of benzodiazepines upon the hypothalamo-hypophyseal-adrenal (HHA) axis activity, the effect of different doses of diazepam (0.1, 1.0 and 10.0 mg/kg) administered 15, 30, 60, 120 and 240 min before decapitation on plasma corticosterone level was studied in rats. While 0.1 mg/kg diazepam had no effect, 1.0 mg/kg diazepam decreased plasma corticosterone levels 30 and 60 min following drug administration. On the other hand, treatment with 10.0 mg/kg diazepam produced an increase in plasma corticosterone levels from 15–120 min following drug administration.

Key words

Diazepam Plasma corticosterone 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abe K, Hiroshige T (1974) Changes in plasma corticosterone and hypothalamic CRF levels following intra-ventricular injection or drug-induced changes of brain biogenic amines in the rat. Neuroendocrinology 14:195–211Google Scholar
  2. Acs Z, Stark E (1978) Possible role of gamma-aminobutyric acid synthesis in the mechanism of dexamethasone feedback action. J. Endocrinol 77:137–141Google Scholar
  3. Barlow SM, Knight AF, Sullivan FM (1979) Plasma corticosterone responses to stress following chronic oral administration of diazepam in the rat. J Pharm Pharmacol 31:23–26Google Scholar
  4. Barett AM, Stockham MA (1963) The effect of housing conditions and simple experimental procedures upon the corticosterone level in the plasma of rats. J Endocrinol 26:97–105Google Scholar
  5. Biswas B, Carlsson A (1978) On the mode of action of diazepam on brain catecholamine metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 303:73–78Google Scholar
  6. Bruni G, Dal Pra P, Dotti MT, Segre G (1980) Plasma ACTH and cortisol levels in benzodiazepine treated rats. Pharmacol Res Commun 12:163–175Google Scholar
  7. Chabot G, Brisette Y, Gascon AL (1982) Relationship between plasma corticosterone and adrenal epinephrine after diazepam treatment in rats. Can J Physiol Pharmacol 60:589–596Google Scholar
  8. Consolo S, Garattini S, Ladinsky H (1975) Action of the Benzodiazepines on cholinergic system. In: Costa E, Greengard P (eds) Advances in biochemical psychopharmacology, vol 14. Raven Press, New York, pp 63–80Google Scholar
  9. Costa E, Guidotti A, Mao CC, Suria A (1975) New concepts on the mechanism of action of benzodiazepines. Life Sci 17:167–186Google Scholar
  10. Fehm HL, Voigt KH, Lang RE, Pfeiffer EF (1980) Effects of neurotransmitters on the release of corticotropin releasing hormone (CRH) by rat hypothalamic tissue in vitro. Exp. Brain Res 39:229–234Google Scholar
  11. Garey AM, Marotta SF (1978) Plasma cortisol of conscious cats during cerebroventricular perfusion with adrenergic, cholinergic and gabanergic antagonists. Neuroendocrinology 25:343–353Google Scholar
  12. Guidotti A, Toffano G, Costa E (1978) An endogenous protein modulates the affinity of GABA and benzodiazepine receptors in the rat brain. Nature 257:553–555Google Scholar
  13. Jones MT, Hillhouse EW, Burden J (1976) Effect of various putative neurotransmitters on the secretion of corticotrophin-releasing hormone from rat hypothalamus in vitro — a model of the neurotransmitters involved. J Endocrinol 69:1–10Google Scholar
  14. Keim KL, Sigg EB (1977) Plasma corticosterone and brain catecholamines in stress: Effect of psychotropic drugs. Pharmacol Biochem Behav 6:79–85Google Scholar
  15. Krulik R, Černy M (1972) Influence of chlordiazepoxide on blood corticosterone under repeated stress. Activitas Nervosa Superior 14:31–34Google Scholar
  16. Lahty RA, Barsuhn C (1974) The effect of minor tranquillizers on stress-induced increases in rat plasma corticosteroids. Psychopharmacologia 35:215–220Google Scholar
  17. Lahty RA, Barsuhn C (1975) The effect of various doses of minor tranquillizers on plasma corticosteroids in stressed rats. Res Commun Chem Pathol Pharmacol 11:595–603Google Scholar
  18. Le Fur G, Guilloux F, Mitrani N, Mizoule J, Uzan A (1979) Relationships between plasma corticosteroids and benzodiazepines in stress. J Pharmacol Exp Ther 211:305–308Google Scholar
  19. Makara GB, Stark E (1974) Effect of gamma-aminobutyric acid (GABA) and GABA antagonist drugs on ACTH release. Neuroendocrinology 16:178–190Google Scholar
  20. Manev H, Peričić D (1983) Hypothalamic GABA system and plasma corticosterone in ether stressed rats. Pharmacol Biochem Behav 18:847–850Google Scholar
  21. Marc V, Morselli PL (1969) Effect of diazepam on plasma corticosterone levels in the rat. J Pharm Pharmacol 21:784–785Google Scholar
  22. Moncloa F, Peron FG, Dorfman RI (1959) The fluorimetric determination of corticosterone in rat adrenal tissue and plasma: Effect of administering ACTH subcutaneously. Endocrinology 65:717–724Google Scholar
  23. Schallek W, Horst WD, Schlosser W (1979) Mechanism of action of benzodiazepines. Adv Pharmacol Chemother 16:45–87Google Scholar
  24. Silber RH, Busch RD, Oslapas R (1958) Practical procedure for estimation of corticosterone or hydrocortisone. Clin Chem 4:278–285Google Scholar
  25. Taylor KM, Laverty R (1969) The effect of chlordiazepoxide, diazepam and nitrazepam on catecholamine metabolism in regions of the rat brain. Eur J Pharmacol 8:296–301Google Scholar
  26. Torellas A, Guaza C, Borrell J (1980) Effects of acute and prolonged administration of chlordiazepoxide upon the pituitary-adrenal activity and brain catecholamines in sound stressed and unstressed rats. Neuroscience 5:2289–2295Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • Danka Peričić
    • 1
  • Nela Lakić
    • 1
  • Hari Manew
    • 1
  1. 1.Department of Experimental Biology and MedicineRudjer Bošković InstituteZagrebYugoslavia

Personalised recommendations