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Research ArticleNEUROPHARMACOLOGY

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gαq and Gα11 Proteins in Rats Undergoing Withdrawal

Gonzalo A. Carrasco, Katerina J. Damjanoska, Deborah N. D'Souza, Yahong Zhang, Francisca Garcia, George Battaglia, Nancy A. Muma and Louis D. Van de Kar
Journal of Pharmacology and Experimental Therapeutics October 2004, 311 (1) 349-355; DOI: https://doi.org/10.1124/jpet.104.069807
Gonzalo A. Carrasco
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Katerina J. Damjanoska
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Deborah N. D'Souza
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Yahong Zhang
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Francisca Garcia
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George Battaglia
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Nancy A. Muma
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Louis D. Van de Kar
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Abstract

One of the characteristics of drug dependence is that a drug has to be administered repeatedly before withdrawal effects can be observed. We have previously shown that withdrawal after 14 days of cocaine treatment produces a supersensitivity of hypothalamic 5-hydroxytryptamine (serotonin) 2A (5-HT2A) receptors, which is accompanied by increases in the levels of Gαq and Gα11 proteins. Unfortunately, the exact duration of cocaine treatment necessary to induce alterations in G protein levels during cocaine withdrawal is unknown. The present study investigated the minimum cocaine treatment period required to produce changes in protein levels of membrane- and cytosol-associated Gαq and Gα11 proteins in the hypothalamic paraventricular nucleus, amygdala, and frontal cortex. Rats were injected with cocaine (15 mg/kg i.p., b.i.d.) for 0, 1, 3, 5, and 7 days and tested after 2 days of withdrawal. The levels of Gαq and Gα11 proteins were increased in the paraventricular nucleus and the amygdala but not in the frontal cortex. Although 1 and 3 days of cocaine treatment were sufficient to maximally elevate the protein levels of Gα11 and Gαq proteins in the amygdala, 5 days of treatment were required to maximally increase the levels of Gα11 and Gαq proteins in the paraventricular nucleus. The data suggest that the amygdala shows a faster neuroadaptation to the effects of cocaine than the hypothalamic paraventricular nucleus. These findings provide insight into the relative importance of individual components of 5-HT2A receptor signal transduction system in regulating the overall sensitivity of this signaling in cocaine-treated rats.

Footnotes

  • This study was supported by United States Health Service Grant DA13669 (to L.D.V.d.K.), MH068612 (to N.A.M.), and DA07741 (to G.B).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

  • doi:10.1124/jpet.104.069807.

  • ABBREVIATIONS: 5-HT, 5-hydroxytryptamine (serotonin); ACTH, adrenocorticotropic hormone; DOI, (±)-1-(2,5 dimethoxy-4-iodophenyl)-2-amino-propane HCl; RGS, regulators of G protein signaling; IOD, integrated optical density; ANOVA, analysis of variance; AGS, activator of G protein signaling; MDL 100,907 (+)-〈-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol.

    • Received April 8, 2004.
    • Accepted June 1, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 311 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 311, Issue 1
1 Oct 2004
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Research ArticleNEUROPHARMACOLOGY

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gαq and Gα11 Proteins in Rats Undergoing Withdrawal

Gonzalo A. Carrasco, Katerina J. Damjanoska, Deborah N. D'Souza, Yahong Zhang, Francisca Garcia, George Battaglia, Nancy A. Muma and Louis D. Van de Kar
Journal of Pharmacology and Experimental Therapeutics October 1, 2004, 311 (1) 349-355; DOI: https://doi.org/10.1124/jpet.104.069807

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Research ArticleNEUROPHARMACOLOGY

Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gαq and Gα11 Proteins in Rats Undergoing Withdrawal

Gonzalo A. Carrasco, Katerina J. Damjanoska, Deborah N. D'Souza, Yahong Zhang, Francisca Garcia, George Battaglia, Nancy A. Muma and Louis D. Van de Kar
Journal of Pharmacology and Experimental Therapeutics October 1, 2004, 311 (1) 349-355; DOI: https://doi.org/10.1124/jpet.104.069807
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