Relationship between incorporation of choline into phosphatidylcholine and morphine binding sites.

Abstract

Calcium (25 mM)-stimulated incorporation of choline into phosphatidylcholine (PC) and 3H-morphine (3H-M) binding was studied using cerebral crude synaptosomal fractions from acute morphine-treated (naive), morphine-dependent and morphine-withdrawn mice. Mice became physically dependent on morphine after ingesting morphine-mixed food. Morphine dependence inhibited the incorporation of 14C-choline into PC. The injection of naloxone (1 mg/kg) to morphine-dependent mice also inhibited the incorporation of 14C-choline into PC. The injection of morphine (10 mg/kg) to morphine-withdrawn mice stimulated the incorporation of 14C-choline into PC, but had no effect, either on acute morphine-treated mice or on morphine-dependent mice. Naloxone (1 mg/kg), morphine (10 mg/kg), morphine dependence and opiate withdrawal (20 hrs after the last exposure to morphine in food) all caused about a 25% decrease in 3H-M (10(-7) M) binding to mouse brain synaptosomes. The injection of 10 mg/kg of morphine 45 min before death caused an additional 20% decrease in 3H-morphine binding in the dependent and withdrawn mice, but not in the naive mice. Stereospecific binding (SSB) of 3H-M was evaluated with respect to: 1) the effect of naloxone treatment in vivo on 3H-M binding in vitro, 2) the effect of morphine treatment in vivo on 3H-M binding in vitro; and 3) the differences between 3H-M bound (in vitro) and both naloxone and morphine treatment (in vivo). SSB activity was high in morphine-withdrawn mice. These differences may be caused by changes in the opiate receptors related to tolerance and withdrawal, and may entail between PC and membrane receptors.