Tzu Chi Medical Journal
Volume 20, Issue 4 , Pages 248-252, December 2008

Cocaine- and Amphetamine-regulated Transcript (CART) Peptide and the Mesolimbic and Nigrostriatal Dopaminergic Systems

  • Shu-Chuan Yang

      Affiliations

    • General Education Center, Tzu Chi College of Technology, Hualien, Taiwan
    • ,
  • Kun-Ruey Shieh

      Affiliations

    • Institute of Neuroscience, Tzu Chi University, Hualien, Taiwan
    • Department of Physiology, Tzu Chi University, Hualien, Taiwan
    • Corresponding Author InformationCorresponding author. Institute of Neuroscience, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, Taiwan

Received 10 March 2008; received in revised form 28 March 2008; accepted 5 April 2008.

Article Outline

Abstract 

Cocaine- and amphetamine-regulated transcript (CART) peptide was discovered in the treatment of cocaine and amphetamine addiction in rats and received its name from this relationship. The functional role of CART peptide is strongly associated with feeding behaviors, and reward and reinforcement. Recently, a number of studies have shown that mesolimbic and nigrostriatal dopaminergic neuronal activities are also under the regulation of CART peptide. In this mini-review, we will introduce the current knowledge on the neuroanatomical, neurochemical and behavioral aspects of interactions of CART peptide with the mesolimbic and nigrostriatal dopamine pathways. Overall, it is clear that there are functional interactions among CART peptide, dopamine, and psychostimulants. The next step is to clarify the receptor(s) and mechanisms of CART peptide to develop potential therapeutic drugs.

Keywords:  Nucleus accumbens , Prefrontal cortex , Striatum

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Spiess J , Villarreal J , Vale W . Isolation and sequence analysis of a somatostatin-like polypeptide from ovine hypothalamus . Biochemistry . 1981;20:1982–1988
  2. Douglass J , McKinzie AA , Couceyro P . PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine . J Neurosci . 1995;15:2471–2481
  3. Hurd YL , Svensson P , Ponten M . The role of dopamine, dynorphin, and CART systems in the ventral striatum and amygdala in cocaine abuse . Ann N Y Acad Sci . 1999;877:499–506
  4. Vrang N , Larsen PJ , Kristensen P . Cocaine-amphetamine regulated transcript (CART) expression is not regulated by amphetamine . Neuroreport . 2002;13:1215–1218
  5. Smith Y , Koylu EO , Couceyro P , et al.   Ultrastructural localization of CART (cocaine- and amphetamine-regulated transcript) peptides in the nucleus accumbens of monkeys . Synapse . 1997;27:90–94
  6. Lakatos A , Prinster S , Vicentic A , et al.   Cocaine- and amphetamine-regulated transcript (CART) peptide activates the extracellular signal-regulated kinase (ERK) pathway in AtT20 cells via putative G-protein coupled receptors . Neurosci Lett . 2005;384:198–202
  7. Vicentic A , Lakatos A , Kuhar MJ . CART (cocaine- and amphetamine-regulated transcript) peptide receptors: specific binding in AtT20 cells . Eur J Pharmacol . 2005;528:188–189
  8. Jones DC , Kuhar MJ . CART receptor binding in primary cell cultures of the rat nucleus accumbens . Synapse . 2008;62:122–127
  9. Kuhar MJ , Dall Vechia SE . CART peptides: novel addiction- and feeding-related neuropeptides . Trends Neurosci . 1999;22:316–320
  10. Kuhar MJ , Adams LD , Hunter RG , et al.   CART peptides . Regul Pept . 2000;89:1–6
  11. Adams LD , Gong W , Vechia SD , et al.   CART: from gene to function . Brain Res . 1999;848:137–140
  12. Thim L , Kristensen P , Larsen PJ , et al.   CART, a new anorectic peptide . Int J Biochem Cell Biol . 1998;30:1281–1284
  13. Smith Y , Kieval J , Couceyro PR , et al.   CART peptideimmunoreactive neurones in the nucleus accumbens in monkeys: ultrastructural analysis, colocalization studies, and synaptic interactions with dopaminergic afferents . J Comp Neurol . 1999;407:491–511
  14. Dallvechia-Adams S , Smith Y , Kuhar MJ . CART peptideimmunoreactive projection from the nucleus accumbens targets substantia nigra pars reticulata neurons in the rat . J Comp Neurol . 2001;434:29–39
  15. Couceyro PR , Koylu EO , Kuhar MJ . Further studies on the anatomical distribution of CART by in situ hybridization . J Chem Neuroanat . 1997;12:229–241
  16. Koylu EO , Couceyro PR , Lambert PD , et al.   Immunohistochemical localization of novel CART peptides in rat hypothalamus, pituitary and adrenal gland . J Neuroendocrinol . 1997;9:823–833
  17. Koylu EO , Couceyro PR , Lambert PD , et al.   Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain . J Comp Neurol . 1998;391:115–132
  18. Dall Vechia S , Lambert PD , Couceyro PC , et al.   CART peptide immunoreactivity in the hypothalamus and pituitary in monkeys: analysis of ultrastructural features and synaptic connections in the paraventricular nucleus . J Comp Neurol . 2000;416:291–308
  19. Elias CF , Lee CE , Kelly JF , et al.   Characterization of CART neurons in the rat and human hypothalamus . J Comp Neurol . 2001;432:1–19
  20. Dallvechia-Adams S , Kuhar MJ , Smith Y . Cocaine- and amphetamine-regulated transcript peptide projections in the ventral midbrain: colocalization with gamma-aminobutyric acid, melanin-concentrating hormone, dynorphin, and synaptic interactions with dopamine neurons . J Comp Neurol . 2002;448:360–372
  21. Kimmel HL , Gong W , Vechia SD , et al.   Intra-ventral tegmental area injection of rat cocaine and amphetamine-regulated transcript peptide 55-102 induces locomotor activity and promotes conditioned place preference . J Pharmacol Exp Ther . 2000;294:784–792
  22. Jaworski JN , Kozel MA , Philpot KB , et al.   Intra-accumbal injection of CART (cocaine-amphetamine regulated transcript) peptide reduces cocaine-induced locomotor activity . J Pharmacol Exp Ther . 2003;307:1038–1044
  23. Jaworski JN , Vicentic A , Hunter RG , et al.   CART peptides are modulators of mesolimbic dopamine and psychostimulants . Life Sci . 2003;73:741–747
  24. Shieh KR . Effects of the cocaine- and amphetamine-regulated transcript peptide on the turnover of central dopaminergic neurons . Neuropharmacology . 2003;44:940–948
  25. Yang SC , Pan JT , Li HY . CART peptide increases the mesolimbic dopaminergic neuronal activity: a microdialysis study . Eur J Pharmacol . 2004;494:179–182
  26. Yang SC , Shieh KR . Differential effects of melanin concentrating hormone on the central dopaminergic neurons induced by the cocaine- and amphetamine-regulated transcript peptide . J Neurochem . 2005;92:637–646
  27. Yang SC , Shieh KR . Gonadal hormones-mediated effects on the stimulation of dopamine turnover in mesolimbic and nigrostriatal systems by cocaine- and amphetamine-regulated transcript (CART) peptide in male rats . Neuropharmacology . 2007;53:801–809
  28. Shieh KR , Yang SC . Effects of estradiol on the stimulation of dopamine turnover in mesolimbic and nigrostriatal systems by cocaine- and amphetamine-regulated transcript peptide in female rats . Neuroscience . 2008;154:1589–1597
  29. Hurd YL , Fagergren P . Human cocaine- and amphetamineregulated transcript (CART) mRNA is highly expressed in limbic- and sensory-related brain regions . J Comp Neurol . 2000;425:583–598
  30. Marie-Claire C , Laurendeau I , Canestrelli C , et al.   Fos but not Cart (cocaine and amphetamine regulated transcript) is overexpressed by several drugs of abuse: a comparative study using real-time quantitative polymerase chain reaction in rat brain . Neurosci Lett . 2003;345:77–80
  31. Yang SC , Shieh KR . Effects of the cocaine- and amphetamineregulated transcript peptide on the turnover of dopamine in tuberoinfundibular neurons and serum prolactin levels: studies using estrogen, melanin concentrating hormone, and melanocortin . Neuropharmacology . 2004;47:1070–1080

PII: S1016-3190(08)60047-6

doi:10.1016/S1016-3190(08)60047-6

Tzu Chi Medical Journal
Volume 20, Issue 4 , Pages 248-252, December 2008

Article Tools