Alterations of synaptic high and low affinity opiate binding sites after acute and chronic morphine administration in mice.
1. The opiate receptor binding to whole brain synaptic membranes obtained from mice subjected to acute and chronic morphine administration and precipitated withdrawal was investigated. 2. The number of high and low affinity binding sites was significantly higher in morphine tolerant group than in control; acute administration of morphine also induced an increase in the number of binding sites, though this increase was significantly lower as compared to tolerant group. 3. The affinity of both high and low affinity sites, however remained unchanged after acute or chronic treatment. In contrast, both the affinity and the number of binding sites were significantly reduced after precipitated withdrawal, compared to the tolerant group. 4. Sodium chloride enhanced the antagonist binding and inhibited the agonist binding in both tolerant and non-tolerant groups. 5. It is concluded that (a) the increase in the number of receptors during tolerance development is an extension of the acute effect of morphine, (b) the character of tolerant membrane is qualitatively same as that of non-tolerant membrane, (c) upon withdrawal, the receptor population is brought back to normal; the altered higher, affinity after withdrawal may be a compensatory effect as a corollary to the withdrawal-induced decrease in receptor population.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004361:Drug Tolerance; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000378:metabolism*; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism
D011957:Receptors, Opioid; D009270:Naloxone; D012965:Sodium Chloride; D009020:Morphine; D004090:Dihydromorphine