Elsevier

Brain Research

Volume 892, Issue 2, 23 February 2001, Pages 376-379
Brain Research

Short communication
Increased midbrain 5-HT1A receptor number and responsiveness in cholestatic rats

https://doi.org/10.1016/S0006-8993(00)03058-4Get rights and content

Abstract

Midbrain somatodendritic 5-HT1A autoreceptors play a central inhibitory role in the regulation of serotonergic neurotransmission. Given that serotonergic neurotransmission appears to be altered in experimental cholestatic liver disease we examined alterations in midbrain 5-HT1A autoreceptor binding and physiological responses in rats with experimental cholestatic liver disease in comparison to non-cholestatic controls. Using a standard receptor binding assay cholestatic rats exhibited an increase in midbrain 5-HT1A receptor number but no change in receptor affinity compared to controls. Midbrain 5-HT1A receptor mRNA expression as determined by semiquantitative RT–PCR was similar in cholestatic and non-cholestatic animals. In addition, cholestatic rats exhibited enhanced 5-HT1A autoreceptor-mediated hypothermic and hyperphagic responses compared to non-cholestatic controls after the administration of the highly specific 5-HT1A receptor agonist LY293284. These findings indicate that experimental cholestatic liver injury is associated with enhanced 5-HT1A autoreceptor-mediated physiological responsiveness in the setting of increased midbrain 5-HT1A receptor number but not affinity.

Section snippets

Acknowledgements

This work was supported by the Medical Research Council (MRC) of Canada. M.G. Swain is an Alberta Heritage Foundation for Medical Research Scholar. K.W. Burak was supported by the Canadian Association for the Study of the Liver (CASL)/MRC/PMAC/Schering Canada Dr Victor Feinman Hepatology Research Fellowship. The authors wish to thank Dr Jon Meddings for his assistance in the analysis of the 5-HT binding assay results.

References (20)

There are more references available in the full text version of this article.

Cited by (0)

View full text