Detection of β-endorphin in the cerebrospinal fluid after intrastriatal microinjection into the rat brain

We have investigated to what extent microinjected β-endorphin could migrate from the rat brain parenchyma into the CSF compartment. Exogenous rat β-endorphin (0.1 nmol) was microinjected into the left striatum 1 mm from the lateral ventricle in anesthetized male rats. CSF samples were collected at different time points up to 2 h post-injection from a catheter affixed to the atlanto-occipital membrane of the cisterna magna. Radioimmunoassay and mass spectrometry were performed on the CSF samples, and brain sections were immunostained for β-endorphin and μ-opioid receptors. The β-endorphin injected rats showed a marked increase in β-endorphin immunoreactive (IR) material in the CSF, with a peak at 30-45 min post-injection, and this β-endorphin-IR material existed mainly as the intact β-endorphin peptide. The immunohistochemistry results revealed the appearance of distinct β-endorphin-IR cell bodies in the globus pallidus and the bed nucleus of stria terminalis supracapsular part, regions distant from the injection site, at 2 h post-injection of exogenous β-endorphin. The β-endorphin-IR in several of the globus pallidus cell bodies colocalized with the μ-opioid receptor-IR at the cell surface. These findings show that upon delivery of synthetic β-endorphin, there is a significant intracerebral spread of the injected peptide, reaching regions far from the site of injection via diffusion in the extracellular space and flow in the cerebrospinal fluid. This may be of relevance when interpreting studies based on intracerebral injections of peptides, and advances our knowledge regarding the migration of compounds within the brain.