Elevated D3 dopamine receptor mRNA in dopaminergic and dopaminoceptive regions of the rat brain in response to morphine.
As opiates increase dopamine transmission, we measured the effects of morphine on dopamine-related genes using a real-time optic PCR assay that reliably detects small differences in mRNA in discrete brain regions. Tissue from dopaminoceptive and dopaminergic brain regions was collected from rats injected twice daily for 7 days with saline or increasing doses of morphine. Tissues were assayed for D1, D2 and D3 dopamine receptor mRNAs (D1R, D2R and D3R), as well as for mRNAs for tyrosine hydroxylase (TH) and the dopamine transporter (DAT). The neuron-associated mRNAs for SNAP-25 and synaptophysin, as well as the glial-associated mRNA for S100-beta and three 'housekeeping' mRNAs, were also measured. As reported previously by others, there was no alteration in D1R mRNA and a 25% decrease in D2R mRNA in the caudate-putamen, 2 h after the final morphine injection. Importantly, in the same RNA extracts, D3R mRNA showed significant increases of 85% in the caudate-putamen and 165% in the ventral midbrain, including the substantia nigra and ventral tegmental area. There were no other significant morphine effects. Mapping of brain regions in saline control rats agreed with previous studies, including showing the presence of low abundance TH mRNA and the absence of DAT mRNA in the caudate-putamen. The finding that chronic, intermittent injections of morphine caused an increase in D3R mRNA extends our understanding of the ability of D3R agonists to reduce the effects of morphine.
Spangler
Rudolph
R
Laboratory of Behavioral Neuroscience, The Rockefeller University, Box 278, 1230 York Avenue, New York, NY 10021, USA. rudolph.spangler@rockefeller.edu
Goddard
Noel L
NL
Avena
Nicole M
NM
Hoebel
Bartley G
BG
Leibowitz
Sarah F
SF
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050637:Receptors, Dopamine D3; D009418:S100 Proteins / Q000235:genetics; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D016708:Synaptophysin / Q000235:genetics; D050825:Synaptosomal-Associated Protein 25; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; C493595:Drd3 protein, rat; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D009418:S100 Proteins; C110294:S100A1 protein; C493216:Slc6a3 protein, rat; C494210:Snap25 protein, rat; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine