A region-specific increase in Galphaq and Galpha11 proteins in brains of rats during cocaine withdrawal.
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, Galphaq, Galpha11, 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 Galphaq and Galpha11 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, Galphaz 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 Galphaq and Galpha11 proteins and not with changes in the expression of 5-HT2A receptors.
Carrasco
Gonzalo A
GA
Department of Pharmacology, Loyola University of Chicago, Stritch School of Medicine, 2160 South First Ave., Maywood, IL 60153, USA.
Zhang
Yahong
Y
Damjanoska
Katerina J
KJ
D'Souza
Deborah N
DN
Garcia
Francisca
F
Battaglia
George
G
Muma
Nancy A
NA
Van de Kar
Louis D
LD
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D007091:Image Processing, Computer-Assisted; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D020710:RGS Proteins / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D020710:RGS Proteins; D044402:Receptor, Serotonin, 5-HT2A; C115771:Rgs7 protein, rat; C098799:RGS4 protein; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D003042:Cocaine