TY - JOUR T1 - A Region-Specific Increase in Gα<sub>q</sub> And Gα<sub>11</sub> Proteins in Brains of Rats during Cocaine Withdrawal JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1012 LP - 1019 DO - 10.1124/jpet.103.056978 VL - 307 IS - 3 AU - Gonzalo A. Carrasco AU - Yahong Zhang AU - Katerina J. Damjanoska AU - Deborah N. D'Souza AU - Francisca Garcia AU - George Battaglia AU - Nancy A. Muma AU - Louis D. Van de Kar Y1 - 2003/12/01 UR - http://jpet.aspetjournals.org/content/307/3/1012.abstract N2 - Serotonin 2A (5-HT2A) receptor-mediated increases in plasma hormone levels become supersensitive after 42 h of withdrawal from cocaine treatment. The present study investigated which components of the 5-HT2A receptor signaling system are associated with this supersensitivity. Rats were injected daily for 14 days with either saline or cocaine (15 mg/kg i.p.) twice a day or were injected using a “binge” protocol (three injections per day, 1 h apart). Rats were sacrificed 2 or 7 days after the last cocaine injection, and the levels of membrane and cytosol-associated 5-HT2A receptors, Gαq, Gα11, regulators of G protein signaling (RGS)4, and RGS7 proteins were assayed in the hypothalamic paraventricular nucleus, amygdala, and frontal cortex using Western blot analysis. Two days of withdrawal from cocaine, administered twice a day or using a binge protocol, produced an increase in membrane-associated Gαq and Gα11 proteins in the paraventricular nucleus and the amygdala (but not in the frontal cortex). This effect was reversible after 7 days of withdrawal. The protein levels of the 5-HT2A receptor, Gαz protein, and RGS4 or RGS7 proteins were not altered by cocaine withdrawal in any of the above-mentioned brain regions. These findings suggest that the supersensitivity of the 5-HT2A receptors, during withdrawal from chronic cocaine, is associated with an increase in membrane-associated Gαq and Gα11 proteins and not with changes in the expression of 5-HT2A receptors. The American Society for Pharmacology and Experimental Therapeutics ER -