Document Detail

Cocaine-mediated supersensitivity of 5-HT2A receptors in hypothalamic paraventricular nucleus is a withdrawal-induced phenomenon.
MedLine Citation:
PMID:  17055657     Owner:  NLM     Status:  MEDLINE    
We previously reported that treatment and withdrawal from cocaine increases: (1) 5-HT2A receptor-mediated neuroendocrine responses, and (2) Galphaq and Galpha11 G-protein levels in the hypothalamic paraventricular nucleus (PVN) at 48 h post-treatment. This study investigates changes in the initial 24 h of withdrawal to discern whether 5-HT2A receptor supersensitivity is due to cocaine treatment or is induced during the withdrawal period. We report here increases in 5-HT2A receptor-mediated neuroendocrine responses only 12 or 24 h post-treatment, but not during the initial 4 h withdrawal period. Levels of membrane- or cytosol-associated Galphaq or Galpha11 proteins in PVN are not altered during the first 24 h of withdrawal. However, the density of 125I-(-)-1-(2,5 dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI)-labeled high-affinity 5-HT2A receptors in PVN increased 35% in rats withdrawn from cocaine for 24 h. These findings demonstrate that cocaine-induced increases in 5-HT2A receptor function in PVN represents a withdrawal-induced phenomena that: (1) is likely attributed to increased G-protein coupled/high-affinity conformational state of the 5-HT2A receptor, and (2) occurs in the absence of changes in the levels of associated G proteins during the first 24 h.
G A Carrasco; L D Van de Kar; N R Sullivan; M Landry; F Garcia; N A Muma; G Battaglia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-10-19
Journal Detail:
Title:  Neuroscience     Volume:  143     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-07     Completed Date:  2007-01-26     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7-13     Citation Subset:  IM    
Department of Pharmacology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
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MeSH Terms
Amphetamines / pharmacokinetics
Blotting, Western / methods
Cocaine / pharmacology*
Corticosterone / blood
Dopamine Uptake Inhibitors / pharmacology*
Drug Interactions
GTP-Binding Protein alpha Subunits / metabolism
Iodine Isotopes / pharmacokinetics
Paraventricular Hypothalamic Nucleus / drug effects*,  metabolism
Protein Binding / drug effects
Radioimmunoassay / methods
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT2A / metabolism*
Serotonin Agonists / pharmacokinetics
Substance Withdrawal Syndrome / metabolism
Time Factors
Grant Support
Reg. No./Substance:
0/Amphetamines; 0/Dopamine Uptake Inhibitors; 0/GTP-Binding Protein alpha Subunits; 0/Iodine Isotopes; 0/Receptor, Serotonin, 5-HT2A; 0/Serotonin Agonists; 50-22-6/Corticosterone; 50-36-2/Cocaine; 64584-34-5/4-iodo-2,5-dimethoxyphenylisopropylamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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