Calcium content and binding in synaptosomal subfractions during chronic morphine treatment

Chronic exposure to morphine in mice produced an increase in Ca(2+) content of synaptosomes, synaptic plasma membranes (SPM), and synaptic vesicles. Ca(2+) binding capacity was significantly reduced in tolerant SPM fractions. Naloxone significantly reversed the increased calcium content and reduced binding capacity of SPM when administered to 72-h-treated mice. Scatchard analysis of binding curves reveals three distinct classes of Ca(2+) binding sites. During tolerance, the high- and low-affinity sites exhibit a reduced capacity to bind calcium, which may be reversed by in vivo and in vitro administration of naloxone. The increase in SPM and synaptic vesicle calcium content may reflect adaptive changes in the cell membrane during tolerance development, which may contribute to changes in neurotransmitter and second messenger function.