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, Louis D. Van De Kar

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15 Scopus citations

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-HT 2A) 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.

Original languageEnglish (US)
Pages (from-to)349-355
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume311
Issue number1
DOIs
StatePublished - Oct 2004

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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