In vivo down-regulation of rat striatal opioid receptors by chronic enkephalin

Administration of methionine enkephalin (ICV) to rats for 5 days resulted in the development of physical dependence as exemplified by a hypothermic response which peaked 2-8 hours after initiation of withdrawal. Twenty-four hours post-withdrawal, opioid receptor binding was determined in the striatum using a selective delta receptor ligand. These studies revealed a decreased in the number of receptors. Bmax decreased from 193 +/- 20.4 fmoles/mg protein in controls to 136 +/- 9.7 fmoles/mg protein in enkephalin treated rats. This difference is significant at p less than 0.001. Existing evidence suggests that this decrease in binding is predominantly due to a decrease in delta receptors. Hence, the present findings indicate that delta receptor down-regulation in vivo may be an important mechanism in the adaptive response to chronic exposure to an endogenous opioid peptide.