Display options
Share it on

Psychopharmacology (Berl). 1992;109(3):305-14. doi: 10.1007/BF02245878.

Desmethylimipramine attenuates cocaine withdrawal in rats.

Psychopharmacology

A Markou, R L Hauger, G F Koob

Affiliations

  1. Department of Neuropharmacology CVN-7, Scripps Research Institute, La Jolla, CA 92037.

PMID: 1365631 DOI: 10.1007/BF02245878

Abstract

Depression and anhedonia are two major symptoms of cocaine withdrawal in humans. Hence, pharmacological treatments effective in depression might also alleviate the symptoms of cocaine withdrawal. In the present study, the effects of acute and repeated administration of a tricyclic antidepressant, desmethylimipramine (DMI), were investigated in naive and cocaine-withdrawing rats. An animal model of cocaine withdrawal was used that employs the elevation in intracranial self-stimulation (ICSS) thresholds following the termination of prolonged periods of cocaine self-administration as a measure of an animal's "anhedonic" state. The influence of chronic DMI treatment on beta-adrenergic receptor binding and affinity was also correlated with the behavioral signs of cocaine withdrawal. Neither acute nor repeated DMI treatment influenced reward functions in rats that were not undergoing cocaine withdrawal. However, repeated DMI treatment significantly down-regulated beta-adrenergic receptors, and shortened the duration of the post-cocaine "anhedonia" (elevation in thresholds). Furthermore, the magnitude of the beta-adrenergic receptor down-regulation correlated significantly with the degree of effectiveness of DMI treatment in reversing the post-cocaine "anhedonia". However, chronic DMI treatment did reduce the amount of cocaine self-administered by the animals. The reversal of the post-cocaine anhedonia in this animal model of cocaine withdrawal by chronic DMI treatment demonstrates the potential usefulness of the model in identifying new pharmacotherapies for cocaine withdrawal. In addition, the results indicate that tricyclic antidepressants may be able to ameliorate some of the symptoms of cocaine withdrawal.

Similar articles

Cited by

Nieto A, Bailey T, Kaczanowska K, McDonald P.
Curr Top Behav Neurosci. 2022;52:81-118. doi: 10.1007/7854_2021_232.
PMID: 34036555

Nieto A, Bailey T, Kaczanowska K, McDonald P.
Curr Top Behav Neurosci. 2021 May 26; doi: 10.1007/7854_2021_232. Epub 2021 May 26.
PMID: 34036555

Nieto A, Bailey T, Kaczanowska K, McDonald P.
Curr Top Behav Neurosci. 2022;52:81-118. doi: 10.1007/7854_2021_232.
PMID: 34036555

References

  1. Pharmacol Biochem Behav. 1980 Sep;13(3):379-83 - PubMed
  2. Naunyn Schmiedebergs Arch Pharmacol. 1987 Feb;335(2):109-14 - PubMed
  3. Neuropsychopharmacology. 1991 Jan;4(1):17-26 - PubMed
  4. Science. 1991 Mar 29;251(5001):1580-6 - PubMed
  5. J Clin Pharmacol. 1987 Aug;27(8):549-54 - PubMed
  6. J Cell Physiol. 1978 Aug;96(2):215-23 - PubMed
  7. Physiol Rev. 1983 Jul;63(3):844-914 - PubMed
  8. Pharmacol Biochem Behav. 1979 Mar;10(3):441-3 - PubMed
  9. Arch Gen Psychiatry. 1986 Feb;43(2):107-13 - PubMed
  10. Psychiatry Res. 1989 Jul;29(1):11-6 - PubMed
  11. Am J Psychiatry. 1965 Nov;122(5):509-22 - PubMed
  12. Neuropharmacology. 1987 Jul;26(7B):815-22 - PubMed
  13. Pharmacol Biochem Behav. 1977 Jul;7(1):59-64 - PubMed
  14. Yale J Biol Med. 1988 Mar-Apr;61(2):123-36 - PubMed
  15. Eur J Pharmacol. 1987 Sep 2;141(1):95-100 - PubMed
  16. Neuropsychopharmacology. 1992 Nov;7(3):213-24 - PubMed
  17. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(5):673-82 - PubMed
  18. Pharmacol Biochem Behav. 1988 May;30(1):1-4 - PubMed
  19. Physiol Behav. 1987;41(4):303-8 - PubMed
  20. Drug Alcohol Depend. 1990 Feb;25(1):21-5 - PubMed
  21. Eur J Pharmacol. 1983 Oct 28;94(3-4):193-201 - PubMed
  22. Psychopharmacology (Berl). 1984;83(1):1-16 - PubMed
  23. J Cyclic Nucleotide Res. 1981;7(5):303-12 - PubMed
  24. Neuropharmacology. 1982 Nov;21(11):1145-9 - PubMed
  25. Science. 1980 Mar 7;207(4435):1093-5 - PubMed
  26. Life Sci. 1985 Feb 4;36(5):443-7 - PubMed
  27. Biol Psychiatry. 1990 Aug 1;28(3):223-30 - PubMed
  28. J Pharmacol Exp Ther. 1990 May;253(2):760-70 - PubMed
  29. Pharmacol Biochem Behav. 1990 Jul;36(3):463-71 - PubMed
  30. Science. 1980 Sep 26;209(4464):1545-6 - PubMed
  31. Psychopharmacology (Berl). 1981;73(4):323-7 - PubMed
  32. Mol Pharmacol. 1989 Jul;36(1):211-8 - PubMed
  33. Mol Pharmacol. 1989 Jul;36(1):201-10 - PubMed
  34. Anal Biochem. 1980 Sep 1;107(1):220-39 - PubMed
  35. Pharmacol Biochem Behav. 1990 Oct;37(2):277-81 - PubMed
  36. Science. 1981 Nov 6;214(4521):683-5 - PubMed
  37. Pharmacol Biochem Behav. 1982 Nov;17(5):901-4 - PubMed
  38. Naunyn Schmiedebergs Arch Pharmacol. 1976 May;293(2):109-14 - PubMed
  39. Annu Rev Psychol. 1981;32:523-74 - PubMed
  40. J Pharmacol Exp Ther. 1984 Mar;228(3):640-7 - PubMed
  41. NIDA Res Monogr. 1987;76:221-5 - PubMed
  42. Neurosci Biobehav Rev. 1983 Spring;7(1):45-72 - PubMed
  43. J Clin Pharmacol. 1986 Mar;26(3):211-4 - PubMed
  44. Brain Res. 1982 Mar;257(1):79-103 - PubMed
  45. J Neural Transm. 1989;76(1):29-38 - PubMed
  46. Fed Proc. 1979 Oct;38(11):2473-6 - PubMed
  47. Arch Gen Psychiatry. 1989 Feb;46(2):117-21 - PubMed
  48. Arch Gen Psychiatry. 1984 Sep;41(9):903-9 - PubMed
  49. Am J Psychiatry. 1983 Nov;140(11):1525-6 - PubMed
  50. Eur J Pharmacol. 1990 May 3;180(1):31-5 - PubMed
  51. Pharmacol Biochem Behav. 1988 Oct;31(2):243-7 - PubMed
  52. Psychosomatics. 1986 Nov;27(11 Suppl):24-9 - PubMed
  53. Physiol Rev. 1984 Apr;64(2):661-743 - PubMed
  54. Eur J Pharmacol. 1981 Sep 11;74(2-3):195-206 - PubMed
  55. Physiol Behav. 1992 Jan;51(1):111-9 - PubMed
  56. Psychopharmacology (Berl). 1990;101(2):208-13 - PubMed
  57. Science. 1988 Nov 4;242(4879):715-23 - PubMed
  58. Lancet. 1972 Sep 23;2(7778):632-5 - PubMed
  59. J Pharmacol Exp Ther. 1978 Nov;207(2):446-57 - PubMed
  60. Experientia. 1984 Nov 15;40(11):1223-6 - PubMed

Substances

MeSH terms

Publication Types

Grant support