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

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 311; no. 1; p. 349
• Main Authors: Gonzalo A. Carrasco, Katerina J. Damjanoska, Deborah N. D'Souza, Yahong Zhang, Francisca Garcia, George Battaglia, Nancy A. Muma, Louis D. Van de Kar
• Format: Journal Article
• Language: English
• Published: American Society for Pharmacology and Experimental Therapeutics 01.10.2004
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.104.069807

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 Gα q and Gα 11 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 Gα q and Gα 11 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 Gα q and Gα 11 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 Gα 11 and Gα q proteins in the amygdala, 5 days of treatment were required to maximally increase the levels of Gα 11 and Gα q 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-HT 2A receptor signal transduction system in regulating the overall sensitivity of this signaling in cocaine-treated rats.