Effects of acute "binge" cocaine on mRNA levels of mu opioid receptor and neuropeptides in dopamine D1 or D3 receptor knockout mice.
In humans, elevations of mu opioid receptor (MOP-r) binding potential (BP) in the frontal cortex (FC) are associated with cocaine craving during early abstinence. In rats, decreases in dopaminergic (DAergic) transmission in the medial FC are associated with increased cocaine-seeking behavior. DA D1 or D3 receptor homozygous knockout (D1-/- or D3-/-) mice offer the opportunity to test the roles of these specific receptors in regulating MOP-r gene expression in response to cocaine. In the present studies, we found an increase in basal MOP-r mRNA levels in the FC of both D1-/- and D3-/- mice compared to wild type controls, with no change in the nucleus accumbens (NAc) core or caudate-putamen (CPu). Acute "binge" cocaine (3 x 15 mg/kg for 2.5 h) returned FC MOP-r mRNA levels in D1-/- or D3-/- mice to those in wild type controls. In the NAc core, the MOP-r mRNA levels after acute "binge" cocaine were decreased in D1-/- mice while increased in D3-/- mice. In the CPu, however, the MOP-r mRNA levels after acute "binge" cocaine were increased in D1-/- mice while decreased in D3-/- mice. We also found a decrease in basal orexin mRNA levels in the lateral hypothalamus of the D3-/- mice, which was unaltered by acute "binge" cocaine. Together, our findings suggest that: (1) both D1 and D3 receptors are involved in FC MOP-r gene regulation; and (2) D1 and D3 receptors play opposite roles in the effects of cocaine on MOP-r gene regulation differentially in the NAc core or CPu.
Zhou
Yan
Y
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10021, USA. zhouya@mail.rockefeller.edu
Adomako-Mensah
Johannes
J
Yuferov
Vadim
V
Ho
Ann
A
Zhang
Jianhua
J
Xu
Ming
M
Kreek
Mary Jeanne
MJ
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003345:Corticosterone / Q000097:blood; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000068797:Orexins; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000172:deficiency*; D050637:Receptors, Dopamine D3 / Q000172:deficiency*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D017450:Receptors, Opioid, mu; D017483:Receptors, Vasopressin; D011333:Pro-Opiomelanocortin; D003042:Cocaine; D003345:Corticosterone