Sustained withdrawal allows normalization of in vivo [11C]N-methylspiperone dopamine D2 receptor binding after chronic binge cocaine: a positron emission tomography study in rats.
In our previous positron emission tomography studies striatal binding for both [11C]SCH23390 and [11C]N-methylspiperone (NMSP) were decreased in the rat brain on the last day of chronic (14 days) binge cocaine administration. We have found that [11C]SCH23390 binding to dopamine D1 receptors returns to saline control levels within ten days withdrawal from chronic binge cocaine and remains at control levels after 21 days withdrawal. An 18% decrease in [11C]NMSP binding to dopamine D2 receptors was observed after ten days withdrawal. However, importantly, after 21 days withdrawal [11C]NMSP binding was at saline control levels. Changes of in vivo [11C]NMSP binding required a longer abstinence period for normalization than [11C]SCH23390 binding. The apparent recovery of dopamine D2 receptors after prolonged abstinence from chronic cocaine and the different rates of normalization for dopamine D1 versus D2 receptors may be critical information for development of pharmacotherapies for cocaine dependent patients.
Maggos
C E
CE
Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA.
Tsukada
H
H
Kakiuchi
T
T
Nishiyama
S
S
Myers
J E
JE
Kreuter
J
J
Schlussman
S D
SD
Unterwald
E M
EM
Ho
A
A
Kreek
M J
MJ
D000704:Analysis of Variance; D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000503:physiopathology*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D002250:Carbon Radioisotopes; D017448:Receptors, Dopamine D2; D013134:Spiperone; C039167:3-N-methylspiperone; D003042:Cocaine