Short-term cocaine treatment causes neuroadaptive changes in Galphaq and Galpha11 proteins in rats undergoing withdrawal.
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 Galpha(q) and Galpha(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 Galpha(q) and Galpha(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 Galpha(q) and Galpha(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 Galpha(11) and Galpha(q) proteins in the amygdala, 5 days of treatment were required to maximally increase the levels of Galpha(11) and Galpha(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.
Carrasco
Gonzalo A
GA
Center for Serotonin Disorders and Department of Pharmacology, Loyola University of Chicago, Stritch School of Medicine, 2160 South First Ave., Maywood, IL 60153, USA.
Damjanoska
Katerina J
KJ
D'Souza
Deborah N
DN
Zhang
Yahong
Y
Garcia
Francisca
F
Battaglia
George
G
Muma
Nancy A
NA
Van de Kar
Louis D
LD
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D018765:Dopamine Uptake Inhibitors; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D003042:Cocaine