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Persistent upregulation of μ‐opioid, but not adenosine, receptors in brains of long‐term withdrawn escalating dose “binge” cocaine‐treated rats
Author(s) -
Bailey Alexis,
Gianotti Robert,
Ho Ann,
Kreek Mary Jeanne
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20168
Subject(s) - downregulation and upregulation , opioid , adenosine , adenosine receptor , receptor , pharmacology , medicine , term (time) , anesthesia , neuroscience , psychology , chemistry , endocrinology , biochemistry , gene , agonist , physics , quantum mechanics
There is evidence showing that the opioid and adenosine systems play an important role in cocaine addiction; fewer studies have examined their roles in cocaine withdrawal. To determine whether cocaine and/or chronic withdrawal from cocaine alters the specific components of the opioid and adenosine systems, we carried out quantitative autoradiographic mapping of μ‐opioid, A 1 and A 2A adenosine receptors in the brains of rats treated with an escalating dose “binge” cocaine administration paradigm and of rats chronically withdrawn from cocaine. Male Fischer rats were injected with saline or cocaine (15 × 3 mg/kg/day for 4 days, 20 × 3 mg/kg/day for 4 days, 25 × 3 mg/kg/day for 4 days and 30 × 3 mg/kg/day for 2 days) at 1‐h intervals for 14 days. Similarly treated rats were withdrawn from that paradigm for 14 days. A significant increase in [ 3 H]DAMGO binding to μ‐receptors was detected in the frontal and cingulate cortex, as well as in the caudate putamen, of long‐term withdrawn rats after an escalating dose “binge” cocaine administration paradigm and in chronic cocaine‐treated rats. No significant cocaine‐induced change was found in A 1 or A 2A receptor binding in any region analyzed. These results reconfirm that μ‐opioid (MOP) receptors undergo upregulation in response to chronic escalating dose “binge” cocaine administration. This upregulation was shown for the first time to persist at least 14 days into withdrawal after escalating “binge” cocaine. Synapse 57:160–166, 2005. © 2005 Wiley‐Liss, Inc.