Mu-opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia.
Pain perception and sensitivity to opiate analgesics strongly depend on genotype. Mice selectively bred for high (HA) and low (LA) swim stress-induced analgesia display markedly divergent morphine analgesia, a difference that appears to be determined by one or at the most two major genes. In an attempt to provide candidate genes mediating the supranormal analgesia displayed by HA mice, we performed mu-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [3H]naloxone. HA mice were found to have significantly higher whole-brain receptor density (Bmax) than LA mice in whole brain homogenates; no significant difference in affinity (Kd) was observed. Quantitative autoradiography confirmed the line difference in whole-brain receptor binding. In the medial thalamus, a brain area implicated in ascending pathways of pain inhibition, HA mice were found to display significantly higher [3H]naloxone binding than C mice (a 64% increase) and LA mice (a 128% increase). No significant line differences were observed in any other brain locus. Thalamic mu receptors may therefore play an important role in a central 'volume control' mechanism of pain inhibition, and underlie individual differences in the responses of mice to opiate analgesic drugs.
Mogil
J S
JS
Research Service (151W), VA Medical Center, Portland, OR 97201.
Marek
P
P
O'Toole
L A
LA
Helms
M L
ML
Sadowski
B
B
Liebeskind
J C
JC
Belknap
J K
JK
D000698:Analgesia; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012641:Selection, Genetic; D013312:Stress, Physiological / Q000503:physiopathology*; D014018:Tissue Distribution; D015854:Up-Regulation
D017450:Receptors, Opioid, mu; D009270:Naloxone