LiCl uncouples signal transduction in morphine-induced supraspinal antinociception in mice.
1. The present study examined whether LiCl antagonism of morphine-induced antinociception in mice occurs at mu-opioid receptors. 2. The antinociceptive ED50 value of intracerebroventricular morphine was maximally increased compared to controls 18 hr after LiCl (10 mmol/kg, s.c.) and remained significantly less (P < 0.05) 7 and 14 days after once-daily LiCl treatment. 3. There was no significant difference in [3H]-[D-Ala2,N-MePhe4,Gly- ol5]enkephalin affinity or receptor density compared to controls (KD = 0.43 nM, Bmax = 54.8 +/- 9.3 pM). 4. These results suggest that LiCl's effect is not on mu-opioid receptors, but rather on some distal site.
Raffa
R B
RB
R. W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776, USA.
Martinez
R P
RP
Renzi
M J
MJ
Codd
E E
EE
D000700:Analgesics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D007276:Injections, Intraventricular; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D000700:Analgesics; D004745:Enkephalins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; D018021:Lithium Chloride