The
opiate withdrawal-like reaction experienced by patients with cholestatic
liver disease after the ingestion of the
opiate antagonist
nalmefene led to the hypothesis that increased opioidergic neurotransmission/neuromodulation in the central nervous system (CNS) contributes to the pathophysiology of
cholestasis. The state of antinociception, which is stereospecifically reversed by
naloxone, documented in rats with
cholestasis from bile duct resection supports this hypothesis. To further study the
opioid system in this animal model of
cholestasis, we studied the release of endogenous
opioid peptides into the extracellular fluid of the dorso-lateral striatum by the technique of in-vivo microdialysis. Total
opioid peptide concentration in the
dialysate was measured by a solid phase radioimmunoassay with an antibody directed against the N-terminus of the
Tyr-Gly-Gly-Phe-X amino acid sequence after acetylation. Basal total
opioid peptide release was significantly higher after surgery in both
sham resected and bile duct resected animals. However, basal (unstimulated) total
opioid peptide release in the striatum of rats was not altered by
cholestasis. It is inferred that the opioidergic abnormalities of
cholestasis are not associated with an appreciable increase in the release of endogenous
opioids into the extracellular fluid of the striatum. Abnormal processing of specific
opioid peptides in
cholestasis however, cannot be excluded.