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NEUROPHARMACOLOGY
q And G11 Proteins in Brains of Rats during Cocaine Withdrawal
Center for Serotonin Disorders Research and Department of Pharmacology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois
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, G
q, G11, 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 Gq and G11 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, Gz 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 Gq and G11 proteins and not with changes in the expression of 5-HT2A receptors.
Address correspondence to: Dr. Louis D. Van de Kar, Department of Pharmacology, Loyola University of Chicago, Stritch School of Medicine, 2160 South First Ave., Maywood, IL 60153. E-mail: lvandek{at}lumc.edu, http://www.luhs.org/SerotoninResearch
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