Regulation of mu-opioid receptor mRNA in rat globus pallidus: effects of enkephalin increases induced by short- and long-term haloperidol administration.
The mRNA encoding mu-opioid receptors is expressed in neurons of the globus pallidus, a region of the basal ganglia that receives a dense enkephalinergic innervation from the striatum. The regulation of the mRNAs encoding the opioid peptide enkephalin in the striatum and the mu-opioid receptor in the globus pallidus was examined with in situ hybridization histochemistry following short- or long-term haloperidol treatments, which alter striatal enkephalin mRNA levels. Animals were administered haloperidol daily for 3 or 7 days (1 mg/kg, s.c.) or continuously for 8 months (1 mg/kg, depot followed by oral). Enkephalin and mu-opioid receptor mRNA levels were unchanged after 3 days of haloperidol treatment. In contrast, the enkephalin mRNA level was increased in the striatum, and mu-opioid receptor mRNA levels were markedly decreased in the globus pallidus after 7 days of haloperidol administration. Similar effects were observed in rats treated with haloperidol for 8 months. The results provide the first evidence of regulation of mu-opioid receptor mRNA in vivo.
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104.
J M
JM
Delfs
L
L
Yu
G D
GD
Ellison
T
T
Reisine
M F
MF
Chesselet
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004334:Drug Administration Schedule; D004745:Enkephalins / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000096:biosynthesis*; D012016:Reference Values; D013997:Time Factors
D004745:Enkephalins; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D006220:Haloperidol