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 o n genotype. Mice selectively bred for high (HA) and low (LA) swim stre ss-induced analgesia display markedly divergent morphine analgesia, a difference that appears to be determined by one or at the most two maj or genes. In an attempt to provide candidate genes mediating the supra normal analgesia displayed by HA mice, we performed mu-opiate receptor binding on 27th generation HA, LA, and control (C) mice using [H-3]na loxone. HA mice were found to have significantly higher whole-brain re ceptor density (B-max) than LA mice in whole brain homogenates; no sig nificant difference in affinity (K-d) was observed. Quantitative autor adiography confirmed the line difference in whole-brain receptor bindi ng. In the medial thalamus, a brain area implicated in ascending pathw ays of pain inhibition, HA mice were found to display significantly hi gher [H-3]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 importa nt role in a central 'volume control' mechanism of pain inhibition, an d underlie individual differences in the responses of mice to opiate a nalgesic drugs.