Persistent upregulation of mu-opioid, but not adenosine, receptors in brains of long-term withdrawn escalating dose "binge" cocaine-treated rats.
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 mu-opioid, A1 and A2A 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in the brains of rats treated with an escalating dose "binge" cocaine administration paradigm and of rats chronically withdrawn from cocaine.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 x 3 mg/kg/day for 4 days, 20 x 3 mg/kg/day for 4 days, 25 x 3 mg/kg/day for 4 days and 30 x 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 Similarly treated rats were withdrawn from that paradigm for 14 days.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to mu-receptors was detected in the frontal and cingulate cortex, as well as in the caudate putamen, of long-term withdrawn rats after an escalating dose "binge" cocaine administration paradigm and in chronic cocaine-treated rats.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 A1 or A2A receptor binding in any region analyzed. These results reconfirm that mu-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.
Bailey
Alexis
A
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10021, USA. a.bailey@surrey.ac.uk
Gianotti
Robert
R
Ho
Ann
A
Kreek
Mary Jeanne
MJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000701:Analgesics, Opioid; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000493:pharmacokinetics; D008297:Male; D010627:Phenethylamines / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D011916:Rats, Inbred F344; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000187:drug effects*; D014970:Xanthines / Q000493:pharmacokinetics
D000701:Analgesics, Opioid; D018765:Dopamine Uptake Inhibitors; D010627:Phenethylamines; D058915:Purinergic P1 Receptor Antagonists; D017450:Receptors, Opioid, mu; D018047:Receptors, Purinergic P1; D014970:Xanthines; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D003042:Cocaine; D000241:Adenosine