TY - JOUR T1 - Short-Term Cocaine Treatment Causes Neuroadaptive Changes in Gα<sub>q</sub> and Gα<sub>11</sub> Proteins in Rats Undergoing Withdrawal JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 349 LP - 355 DO - 10.1124/jpet.104.069807 VL - 311 IS - 1 AU - Gonzalo A. Carrasco AU - Katerina J. Damjanoska AU - Deborah N. D'Souza AU - Yahong Zhang AU - Francisca Garcia AU - George Battaglia AU - Nancy A. Muma AU - Louis D. Van de Kar Y1 - 2004/10/01 UR - http://jpet.aspetjournals.org/content/311/1/349.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -