Excess release of substance P from the spinal cord of mice during morphine withdrawal and involvement of the enhancement of presynaptic Ca2+ entry.
Possible presynaptic mechanisms involved in the naloxone-precipitated withdrawal jumping in morphine-dependent mice were studied. The withdrawal jumping precipitated by intrathecally (i.t.) administered naloxone (10 nmol) was abolished by the i.t. pretreatment with a substance P antagonist, [D-Pro4,D-Trp7,9,10]-substance P4-11 (10 nmol). The high KCl-evoked 45Ca2+ entry into synaptosomes and the release of immunoreactive substance P from slices were significantly enhanced by 10(-4) M naloxone in the morphine pelleted spinal cord, but not in the vehicle pelleted ones. These findings suggest that naloxone activates the depolarization-evoked Ca2+ entry into the nerve terminals, enhances the release of substance P from the spinal cord and the induction of withdrawal jumping in morphine-dependent mice then follows.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000009:adverse effects*; D013116:Spinal Cord / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D013373:Substance P; D009020:Morphine; D002118:Calcium