Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Mar 15;88(6):2078–2082. doi: 10.1073/pnas.88.6.2078

Cocaine-induced reduction of brain neuropeptide Y synthesis dependent on medial prefrontal cortex.

C Wahlestedt 1, F Karoum 1, G Jaskiw 1, R J Wyatt 1, D Larhammar 1, R Ekman 1, D J Reis 1
PMCID: PMC51172  PMID: 2006146

Abstract

Repeated administration of cocaine elicits substantial, long-lasting, but reversible reductions in neuropeptide Y (NPY) and NPY mRNA in the rat cerebral cortex and nucleus accumbens. The NPY reduction appears to be mediated through a decrease in NPY biosynthesis, occurring transneuronally, perhaps in response to changes in synaptic dopamine associated with mesolimbic and mesocortical dopamine neurons. The medial prefrontal cortex appears necessary for maintenance of cocaine's action on this neuronal network since excitotoxic lesions of this area prevented (lesion before cocaine) and reversed (lesion after cocaine) the reductions in NPY elicited by the cocaine. NPY may be a sensitive marker for chronic cocaine use. Its decrease may relate to the anxiety and depression associated with cocaine withdrawal in humans.

Full text

PDF
2078

Images in this article

2079Image
on p.2079

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aoki C., Pickel V. M. Neuropeptide Y-containing neurons in the rat striatum: ultrastructure and cellular relations with tyrosine hydroxylase- containing terminals and with astrocytes. Brain Res. 1988 Sep 6;459(2):205–225. doi: 10.1016/0006-8993(88)90637-3. [DOI] [PubMed] [Google Scholar]
  2. Axelrod J. Noradrenaline: fate and control of its biosynthesis. Science. 1971 Aug 13;173(3997):598–606. doi: 10.1126/science.173.3997.598. [DOI] [PubMed] [Google Scholar]
  3. Beal M. F., Frank R. C., Ellison D. W., Martin J. B. The effect of neuropeptide Y on striatal catecholamines. Neurosci Lett. 1986 Oct 30;71(1):118–123. doi: 10.1016/0304-3940(86)90267-3. [DOI] [PubMed] [Google Scholar]
  4. DENGLER H. J., SPIEGEL H. E., TITUS E. O. Effects of drugs on uptake of isotopic norepinephrine by cat tissues. Nature. 1961 Aug 19;191:816–817. doi: 10.1038/191816a0. [DOI] [PubMed] [Google Scholar]
  5. Ekblad E., Arnbjörnsson E., Ekman R., Håkanson R., Sundler F. Neuropeptides in the human appendix. Distribution and motor effects. Dig Dis Sci. 1989 Aug;34(8):1217–1230. doi: 10.1007/BF01537270. [DOI] [PubMed] [Google Scholar]
  6. Ekman R., Tornqvist K. Glucagon and VIP in the retina. Invest Ophthalmol Vis Sci. 1985 Oct;26(10):1405–1409. [PubMed] [Google Scholar]
  7. Gawin F. H., Kleber H. D. Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Clinical observations. Arch Gen Psychiatry. 1986 Feb;43(2):107–113. doi: 10.1001/archpsyc.1986.01800020013003. [DOI] [PubMed] [Google Scholar]
  8. Goeders N. E. Intracranial cocaine self-administration. NIDA Res Monogr. 1988;88:199–216. [PubMed] [Google Scholar]
  9. Goeders N. E., Smith J. E. Cortical dopaminergic involvement in cocaine reinforcement. Science. 1983 Aug 19;221(4612):773–775. doi: 10.1126/science.6879176. [DOI] [PubMed] [Google Scholar]
  10. Heilig M., Vècséi L., Wahlestedt C., Alling C., Widerlöv E. Effects of centrally administered neuropeptide Y (NPY) and NPY13-36 on the brain monoaminergic systems of the rat. J Neural Transm Gen Sect. 1990;79(3):193–208. doi: 10.1007/BF01245130. [DOI] [PubMed] [Google Scholar]
  11. Hurd Y. L., Weiss F., Koob G. F., And N. E., Ungerstedt U. Cocaine reinforcement and extracellular dopamine overflow in rat nucleus accumbens: an in vivo microdialysis study. Brain Res. 1989 Sep 25;498(1):199–203. doi: 10.1016/0006-8993(89)90422-8. [DOI] [PubMed] [Google Scholar]
  12. Kerkerian L., Bosler O., Pelletier G., Nieoullon A. Striatal neuropeptide Y neurones are under the influence of the nigrostriatal dopaminergic pathway: immunohistochemical evidence. Neurosci Lett. 1986 May 6;66(1):106–112. doi: 10.1016/0304-3940(86)90174-6. [DOI] [PubMed] [Google Scholar]
  13. Koob G. F., Bloom F. E. Cellular and molecular mechanisms of drug dependence. Science. 1988 Nov 4;242(4879):715–723. doi: 10.1126/science.2903550. [DOI] [PubMed] [Google Scholar]
  14. Larhammar D., Ericsson A., Persson H. Structure and expression of the rat neuropeptide Y gene. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2068–2072. doi: 10.1073/pnas.84.7.2068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Li S., Pelletier G. The role of dopamine in the control of neuropeptide Y neurons in the rat arcuate nucleus. Neurosci Lett. 1986 Aug 15;69(1):74–77. doi: 10.1016/0304-3940(86)90417-9. [DOI] [PubMed] [Google Scholar]
  16. Risner M. E., Jones B. E. Intravenous self-administration of cocaine and norcocaine by dogs. Psychopharmacology (Berl) 1980;71(1):83–89. doi: 10.1007/BF00433258. [DOI] [PubMed] [Google Scholar]
  17. Ritz M. C., Lamb R. J., Goldberg S. R., Kuhar M. J. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science. 1987 Sep 4;237(4819):1219–1223. doi: 10.1126/science.2820058. [DOI] [PubMed] [Google Scholar]
  18. Salin P., Kerkerian L., Nieoullon A. Expression of neuropeptide Y immunoreactivity in the rat nucleus accumbens is under the influence of the dopaminergic mesencephalic pathway. Exp Brain Res. 1990;81(2):363–371. doi: 10.1007/BF00228127. [DOI] [PubMed] [Google Scholar]
  19. Sivam S. P. Cocaine selectively increases striatonigral dynorphin levels by a dopaminergic mechanism. J Pharmacol Exp Ther. 1989 Sep;250(3):818–824. [PubMed] [Google Scholar]
  20. Sundler F., Håkanson R., Ekblad E., Uddman R., Wahlestedt C. Neuropeptide Y in the peripheral adrenergic and enteric nervous systems. Int Rev Cytol. 1986;102:243–269. doi: 10.1016/s0074-7696(08)61277-2. [DOI] [PubMed] [Google Scholar]
  21. Tatsuoka Y., Riskind P. N., Beal M. F., Martin J. B. The effect of amphetamine on the in vivo release of dopamine, somatostatin and neuropeptide Y from rat caudate nucleus. Brain Res. 1987 May 12;411(1):200–203. doi: 10.1016/0006-8993(87)90702-5. [DOI] [PubMed] [Google Scholar]
  22. Vallejo M., Carter D. A., Biswas S., Lightman S. L. Neuropeptide Y alters monoamine turnover in the rat brain. Neurosci Lett. 1987 Jan 14;73(2):155–160. doi: 10.1016/0304-3940(87)90010-3. [DOI] [PubMed] [Google Scholar]
  23. Wahlestedt C., Ekman R., Widerlöv E. Neuropeptide Y (NPY) and the central nervous system: distribution effects and possible relationship to neurological and psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(1-2):31–54. doi: 10.1016/0278-5846(89)90003-1. [DOI] [PubMed] [Google Scholar]
  24. Wallengren J., Ekman R., Sundler F. Occurrence and distribution of neuropeptides in the human skin. An immunocytochemical and immunochemical study on normal skin and blister fluid from inflamed skin. Acta Derm Venereol. 1987;67(3):185–192. [PubMed] [Google Scholar]
  25. Widerlöv E., Lindström L. H., Wahlestedt C., Ekman R. Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively. J Psychiatr Res. 1988;22(1):69–79. doi: 10.1016/0022-3956(88)90030-1. [DOI] [PubMed] [Google Scholar]
  26. Wyatt R. J., Karoum F., Suddath R., Fawcett R. Persistently decreased brain dopamine levels and cocaine. JAMA. 1988 May 27;259(20):2996–2996. [PubMed] [Google Scholar]
  27. Yokel R. A., Wise R. A. Increased lever pressing for amphetamine after pimozide in rats: implications for a dopamine theory of reward. Science. 1975 Feb 14;187(4176):547–549. doi: 10.1126/science.1114313. [DOI] [PubMed] [Google Scholar]
  28. de Quidt M. E., Emson P. C. Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system--II. Immunohistochemical analysis. Neuroscience. 1986 Jul;18(3):545–618. doi: 10.1016/0306-4522(86)90057-6. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES