Role of Endothelin Receptor Subtypes in the Behavioral Effects of the Intracerebroventricular Administration of Endothelin-1 in Conscious Rats

Abstract

The role of endothelin receptor subtypes, i.e., ET A and ET B receptors, in the behavioral effects of the intracerebroventricular (ICV) administration of endothelin-1 were examined in conscious rats. ICV administration of endothelin-1 (1–9 pmol/rat) dose dependently produced barrel rolling and other convulsive behaviors including bodily twitching, rigidity, back crawling, fore/hindlimb dystonia, fore/hindlimb clonus, tail extension, and facial clonus. Moreover, a marked increase in spontaneous locomotor activity was observed in animals that were treated with a low dose of endothelin-1 (1 pmol/rat, ICV). Endothelin-1 (9 pmol/rat, ICV)-induced barrel rolling and other convulsive behaviors were completely suppressed by the coadministration of BQ-123 (15 nmol, ICV), a specific endothelin ET A receptor antagonist, but not of BQ-788 (15 nmol/rat, ICV), a specific endothelin ET B receptor antagonist. In contrast, increased locomotor activity produced by treatment with a low dose of endothelin-1 (1 pmol/rat, ICV) was antagonized by coadministration of BQ-788, but not of BQ-123. These results indicate that endothelin-1, which has affinity for both endothelin ET A and ET B receptors, most likely acts on central ET A receptors to evoke barrel rolling and other convulsive behaviors. In addition, activation of central ET B receptors may be involved in the increase in spontaneous locomotor activity. These results suggest that brain endothelin receptor subtypes may be involved in the regulation of various physiological functions.