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Research ArticleNEUROPHARMACOLOGY

Intra-Ventral Tegmental Area Injection of Rat Cocaine and Amphetamine-Regulated Transcript Peptide 55-102 Induces Locomotor Activity and Promotes Conditioned Place Preference

Heather L. Kimmel, Wenhe Gong, Stephanie Dall Vechia, Richard G. Hunter and Michael J. Kuhar
Journal of Pharmacology and Experimental Therapeutics August 2000, 294 (2) 784-792;
Heather L. Kimmel
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Wenhe Gong
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Stephanie Dall Vechia
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Richard G. Hunter
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Michael J. Kuhar
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Abstract

Cocaine- and amphetamine-regulated transcript (CART) is a novel mRNA that has been reported to be increased by acute psychostimulant administration, and that may be involved in the effects of psychostimulants. In this study, we examined the effect of centrally administered CART peptides on locomotor activity and conditioned place preference in the rat. CART peptide fragments were bilaterally injected into the ventral tegmental area. CART 55-102 (0.2–5.0 μg/side), an endogenously occurring peptide, dose dependently increased locomotor activity, whereas CART 1-26 (0.1–2.5 μg/side; not found endogenously) did not. The locomotor effects of CART 55-102 were dose dependently blocked by the dopamine D2 receptor antagonist haloperidol (0.03–1.0 mg/kg i.p.). Four injections of 1.0 μg/side CART 55-102 induced a significant place preference, suggesting that CART 55-102 is reinforcing. Increases in locomotor activity after each of these CART 55-102 injections were similar and did not show tolerance or sensitization. This treatment regimen of CART 55-102 also did not produce sensitization to locomotor activity after a subsequent challenge with cocaine or amphetamine. When CART 55-102 (0.2–1.0 μg/side) was injected into the substantia nigra, no significant change in motor activity was observed. However, a higher dose of CART 55-102 (5.0 μg/side) induced a delayed increase in motor activity, suggesting a possible diffusion from the substantia nigra into the ventral tegmental area. Our findings suggest that CART 55-102 is behaviorally active and may be involved in the actions of psychostimulants. This is the first demonstration of the psychostimulant-like effects of CART peptides.

Footnotes

  • Send reprint requests to: Heather L. Kimmel, Ph.D., Yerkes Regional Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA 30329. E-mail: hlkimme{at}emory.edu

  • ↵1 This study was supported by National Institutes of Health Grants RR00165, DA00418, DA10732, and DA005935.

  • Abbreviations:
    CART
    cocaine- and amphetamine-regulated transcript
    VTA
    ventral tegmental area
    GABA
    γ-aminobutyric acid
    CPP
    conditioned place preference
    SN
    substantia nigra
    • Received February 9, 2000.
    • Accepted May 4, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 2
1 Aug 2000
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Research ArticleNEUROPHARMACOLOGY

Intra-Ventral Tegmental Area Injection of Rat Cocaine and Amphetamine-Regulated Transcript Peptide 55-102 Induces Locomotor Activity and Promotes Conditioned Place Preference

Heather L. Kimmel, Wenhe Gong, Stephanie Dall Vechia, Richard G. Hunter and Michael J. Kuhar
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 784-792;

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Research ArticleNEUROPHARMACOLOGY

Intra-Ventral Tegmental Area Injection of Rat Cocaine and Amphetamine-Regulated Transcript Peptide 55-102 Induces Locomotor Activity and Promotes Conditioned Place Preference

Heather L. Kimmel, Wenhe Gong, Stephanie Dall Vechia, Richard G. Hunter and Michael J. Kuhar
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 784-792;
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