TY - JOUR
T1 - Increases in dopamine D3 receptor binding in rats receiving a cocaine challenge at various time points after cocaine self-administration
T2 - Implications for cocaine-seeking behavior
AU - Neisewander, Janet
AU - Fuchs, Rita A.
AU - Tran-Nguyen, Ly T L
AU - Weber, Suzanne M.
AU - Coffey, Greg P.
AU - Joyce, Jeffrey N.
N1 - Funding Information:
We thank Han Ryoo, Taline Khroyan, and Arturo Zavala for their expert technical assistance, and Andrea Alleweireldt for comments on an earlier version of the manuscript. This research was supported by USPHS Grants DA11064, DA05816, and NS40669, and the Howard Hughes Medical Institute through the Undergraduate Biological Sciences Education Program.
PY - 2004/8
Y1 - 2004/8
N2 - Previous research suggests that cocaine dysregulates dopamine D3 receptors. The present study examined the time course of changes in dopamine D3 receptor binding after terminating a cocaine self-administration regimen. [125I]-7-hydroxy-2-[N-propyl-N-(3′-iodo-2′- propenyl)-amino]-tetralin was used to label dopamine D3 receptors in rats that had undergone testing for cocaine-seeking behavior reinstated by a cocaine priming injection (15 mg/kg, i.p.; the behavior results have been previously published), and were killed 24 h after the test at time points that were either 2, 8, or 31-32 days after their last cocaine self-administration session. The results indicated a time-dependent increase in D3 receptor binding relative to controls that received saline yoked to the delivery of cocaine in an experimental animal. Specifically, there was no significant change in D3 receptor binding in cocaine-experienced rats killed at the 2- or 8-day time points relative to controls, but there was an increase in D3 receptor binding in the nucleus accumbens core and ventral caudate-putamen in rats killed at the 31- to 32-day time point. In a subsequent experiment, we replicated the increase in D3 receptor binding in rats that underwent a less extensive self-administration regimen, then were tested for cocaine-primed reinstatement of cocaine-seeking behavior, and then were killed 24 h later at a time point of 22 days after their last self-administration session, Furthermore, the increase in binding was attenuated by repeated 7-hydroxy-N,N-di-n-propyl-2-aminotetralin administration (1 mg/kg/day, s.c. for 14 days), a regimen that also reduces cocaine-seeking behavior in animals when tested in a nondrug state. Collectively, the findings suggest that regulatory responses of D3 receptors may be functionally related to changes in propensity for cocaine-seeking behavior.
AB - Previous research suggests that cocaine dysregulates dopamine D3 receptors. The present study examined the time course of changes in dopamine D3 receptor binding after terminating a cocaine self-administration regimen. [125I]-7-hydroxy-2-[N-propyl-N-(3′-iodo-2′- propenyl)-amino]-tetralin was used to label dopamine D3 receptors in rats that had undergone testing for cocaine-seeking behavior reinstated by a cocaine priming injection (15 mg/kg, i.p.; the behavior results have been previously published), and were killed 24 h after the test at time points that were either 2, 8, or 31-32 days after their last cocaine self-administration session. The results indicated a time-dependent increase in D3 receptor binding relative to controls that received saline yoked to the delivery of cocaine in an experimental animal. Specifically, there was no significant change in D3 receptor binding in cocaine-experienced rats killed at the 2- or 8-day time points relative to controls, but there was an increase in D3 receptor binding in the nucleus accumbens core and ventral caudate-putamen in rats killed at the 31- to 32-day time point. In a subsequent experiment, we replicated the increase in D3 receptor binding in rats that underwent a less extensive self-administration regimen, then were tested for cocaine-primed reinstatement of cocaine-seeking behavior, and then were killed 24 h later at a time point of 22 days after their last self-administration session, Furthermore, the increase in binding was attenuated by repeated 7-hydroxy-N,N-di-n-propyl-2-aminotetralin administration (1 mg/kg/day, s.c. for 14 days), a regimen that also reduces cocaine-seeking behavior in animals when tested in a nondrug state. Collectively, the findings suggest that regulatory responses of D3 receptors may be functionally related to changes in propensity for cocaine-seeking behavior.
KW - 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT)
KW - Abstinence
KW - Cocaine withdrawal
KW - Regulation
KW - Repeated administration
KW - Time-dependent
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U2 - 10.1038/sj.npp.1300456
DO - 10.1038/sj.npp.1300456
M3 - Article
C2 - 15100700
AN - SCOPUS:3242791690
SN - 0893-133X
VL - 29
SP - 1479
EP - 1487
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 8
ER -