Effects of acute and chronic morphine treatments on calcium localization and binding in brain

Acute subcutaneous injection of 25 mg/kg of morphine in rats decreased synaptosomal CA⁺⁺ levels by 29% without altering the Ca⁺⁺ content of other subcellular fractions. In contrast, chronic morphine treatment of mice or rats by pellet implantation selectively increased synaptosomal Ca⁺⁺ levels by almost 100%. This increase in Ca⁺⁺ induced by morphine was blocked by simultaneous chronic administration of naloxone. The binding of low concentrations (10^-7-10^-5 M) of ⁴⁵Ca⁺⁺ to synaptic plasma membranes was increased by acute morphine treatment and decreased by chronic administration. The binding of higher concentrations (10^-3 M) of ⁴⁵Ca⁺⁺ to synaptic vesicles was also increased by acute morphine treatment and decreased by chronic treatment. Changes in binding were not observed with other subcellular fractions. It is suggested that these highly selective changes in Ca⁺⁺ levels and binding may represent mechanisms by which acute morphine treatment interferes with synaptic transmission and by which chronic administration overcomes these effects, resulting in tolerance and dependence.