Download PDF
Horm Metab Res 2001; 33(9): 554-558
DOI: 10.1055/s-2001-17205
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

Cocaine-Amphetamine-Regulated Transcript Influences Energy Metabolism, Anxiety and Gastric Emptying in Mice

A. Asakawa 1 , A. Inui 1 , H. Yuzuriha 1 , T. Nagata 1 , T. Kaga 1 , N. Ueno 1 , M. A. Fujino 2 , M. Kasuga 1
  • 1 Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe, Japan
  • 2 First Department of Internal Medicine, Yamanashi Medical University, Tamaho, Nakakoma, Yamanashi, Japan
Further Information

Publication History

Publication Date:
17 September 2001 (online)

Also available at
    Permissions and Reprints

This study was designed to investigate the effects of cocaine-amphetamine-regulated transcript (CART), a recently discovered hypothalamic neuropeptide, on food intake, anxiety, oxygen consumption and gastric emptying in mice. Intracerebroventricular (i. c. v.) injection of CART (1 - 100 pmol) markedly reduced food intake in a dose-related manner. A significant decrease was observed 20 min after i. c. v. injection of CART and continued for four hours. In the elevated plus maze test, i. c. v. CART injection significantly raised the normal preference for the closed arms. Furthermore, the i. c. v. injection of CART significantly reduced oxygen consumption and gastric emptying rate. These results suggest that CART modulates feeding, emotion, and autonomic functions in mice.

Key words:

Anxiogenic - Cocaine-Amphetamine-Regulated Transcript - Feeding - Gastric Emptying - Intracerebroventricular - Mice - Oxygen Consumption

References

  • 1 Douglass J, Mckinzie A A, Couceyro P. PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine.  J Neurosci. 1995;  15 2471-2481
    PubMedGoogle Scholar
  • 2 Koylu E O, Couceyro P R, Lambert P D, Ling N C, DeSouza E B, Kuhar M J. Immunohistochemical localization of novel CART peptides in rat hypothalamus, pituitary and adrenal gland.  J Neuroendocrinol. 1997;  9 823-833
    CrossrefPubMedGoogle Scholar
  • 3 Vrang N, Larsen P J, Clausen J T, Kristensen P. Neurochemical characterization of hypothalamic cocaine- amphetamine-regulated transcript neurons.  J Neurosci. 1999;  19 1-8
    PubMedGoogle Scholar
  • 4 Couceyro P R, Koylu E O, Kuhar M J. Further studies on the anatomical distribution of CART by in situ hybridization.  J Chem Neuroanat. 1997;  12 229-241
    CrossrefPubMedGoogle Scholar
  • 5 Koylu E O, Couceyro P R, Lambert P D, Kuhar M J. Cocaine- and amphetamine-regulated transcript peptide immunohistochemical localization in the rat brain.  J Comp Neurol. 1998;  391 115-132
    CrossrefPubMedGoogle Scholar
  • 6 Kristensen P, Judge M E, Thim L, Ribel U, Christjansen K N, Wulff B S, Clausen J T, Jensen P B, Madsen O D, Vrang N, Larsen P J, Hastrup S. Hypothalamic CART is a new anorectic peptide regulated by leptin.  Nature. 1998;  393 72-76
    CrossrefPubMedGoogle Scholar
  • 7 Lambert P D, Couceyro P R, McGirr K M, Dall Vechia S E, Smith Y, Kuhar M J. CART peptides in the central control of feeding and interactions with neuropeptide Y.  Synapse. 1998;  29 293-298
    CrossrefPubMedGoogle Scholar
  • 8 Elias C F, Lee C, Kelly J, Aschkenasi C, Ahima R S, Couceyro P R, Kuhar M J, Saper C B, Elmquist J K. Leptin activates hypothalamic CART neurons projecting to the spinal cord.  Neuron. 1998;  21 1375-1385
    CrossrefPubMedGoogle Scholar
  • 9 Phillips R J, Powley T L. Gastric volume rather than nutrient content inhibits food intake.  Am J Physiol. 1996;  271 R766-R779
    PubMedGoogle Scholar
  • 10 Asakawa A, Inui A, Momose K, Ueno N, Fujino M A, Kasuga M. Endomorphins have orexigenic and anxiolytic activities in mice.  Neuroreport. 1998;  9 2265-2267
    PubMedGoogle Scholar
  • 11 Hirosue Y, Inui A, Teranishi A, Miura M, Nakajima M, Okita M, Nakajima Y, Himori N, Baba S, Kasuga M. Cholecystokinin octapeptide analogues suppress food intake via central CCK-A receptors in mice.  Am J Physiol. 1993;  265 R481-R486
    PubMedGoogle Scholar
  • 12 Nakajima M, Inui A, Teranishi A, Miura M, Hirosue Y, Okita M, Himori N, Baba S, Kasuga M. Effects of pancreatic polypeptide family peptides on feeding and learning behavior in mice.  J Pharmacol Exp Ther. 1994;  268 1010-1014
    PubMedGoogle Scholar
  • 13 Inui A. Feeding and body-weight regulation by hypothalamic neuropeptides-mediation of the actions of leptin.  Trends Neurosci. 1999;  22 62-67
    CrossrefPubMedGoogle Scholar
  • 14 Inui A. Transgenic approach to the study of body weight regulation.  Pharamcol Rev. 2000;  52 35-62
    PubMedGoogle Scholar
  • 15 Rolla M, Andreoni A, Bellitti D, Ferdeghini M, Ghigo E, Muller E E. Corticotrophin-releasing hormone dose not inhibit growth hormone-releasing hormone-induced release of growth hormone in control subjects but is effective in patients with eating disorders.  J Endocrinol. 1994;  140 327-332
    PubMedGoogle Scholar
  • 16 Kaye W H. Neuropeptide abnormalities in anorexia nervosa.  Psychiatry Res. 1996;  62 65-74
    CrossrefPubMedGoogle Scholar
  • 17 Montgomery K C. The relation between fear induced by novel stimulation and exploratory behavior.  J Comp Physiol Psychol. 1958;  48 254-260
    PubMedGoogle Scholar
  • 18 Momose K, Inui A, Asakawa A, Ueno N, Nakajima M, Fujimiya M, Kasuga M. Intracerebroventricularly administered corticotropin-releasing factor inhibits food intake and produces anxiety-like behaviour at very low doses in mice.  Diab Obes Metab. 1999;  1 281-284
    PubMedGoogle Scholar
  • 19 Walker H C, Romsos D R. Similar effects of NPY on energy metabolism and on plasma insulin in adrenalectomized ob/ob and lean mice.  Am J Physiol. 1993;  264 E226-E230
    PubMedGoogle Scholar
  • 20 Asakawa A, Inui A, Ueno N, Fujimiya M, Fujino M A, Kasuga M. Endomorphin-1, an endogenous mu-opioid receptor-selective agonist, stimulates oxygen consumption in mice.  Horm Metab Res. 2000;  32 51-52
    PubMedGoogle Scholar
  • 21 Drescher V S, Chen H L, Romsos D R. Corticotropin-releasing hormone decreases feeding oxygen consumption and activity of genetically obese (ob/ob) and lean mice.  J Nutrition. 1994;  124 524-530
    PubMedGoogle Scholar
  • 22 Vrang N, Tang C M, Larsen P J, Kristensen P. Recombinant CART peptide induces c-Fos expression in central areas involved in control of feeding behaviour.  Brain Res. 1999;  818 499-509
    CrossrefPubMedGoogle Scholar
  • 23 Phillips R J, Powley T L. Gastric volume rather than nutrient content inhibits food intake.  Am J Physiol. 1996;  271 R766-R779
    PubMedGoogle Scholar
  • 24 Duggan J P, Booth D A. Obesity, overeating and rapid gastric emptying in rats with ventromedial hypothalamic lesions.  Science. 1986;  231 609-611
    PubMedGoogle Scholar
  • 25 Asakawa A, Inui A, Ueno N, Makino S, Fujino M A, Kasuga M. Urocortin reduces food intake and gastric emptying in lean and ob/ob obese mice.  Gastroenterology. 1999;  116 1287-1292
    PubMedGoogle Scholar
  • 26 Okumura T, Yamada H, Motomura W, Kohgo Y. Cocaine-amphetamine-regulated transcript (CART) acts in the central nervous system to inhibit gastric acid secretion via brain corticotropin-releasing factor system.  Endocrinology. 2000;  141 2854-2860
    CrossrefPubMedGoogle Scholar
  • 27 Vrang N, Larsen P J, Kristensen P, Tang-Christensen M. Central administration of cocaine-amphetamine-regulated transcript activates hypothalamic neuroendocrine neurons in the rat.  Endocrinology. 2000;  141 794-801
    CrossrefPubMedGoogle Scholar
  • 28 Broberger C, Holmberg K, Kuhar M J, Hokfelt T. Cocaine- and amphetamine-regulated transcript in the rat vagus nerve: A putative mediator of cholecystokinin-induced satiety.  Proc Natl Acad Sci USA. 1999;  96 13 506-13 511
    PubMedGoogle Scholar

A. Inui,M.D., Ph.D. 

Second Department of Internal Medicine
Kobe University School of Medicine

7-5-2 Kusunoki-cho, Chuo-ku
Kobe 650-0017
Japan


Phone: + 81 (78) 382-5862

Fax: + 81 (78) 382-2080

Email: inui@med.kobe-u.ac.jp

      >