Role of endothelin receptor subtypes in the behavioral effects of the intracerebroventricular administration of endothelin-1 in conscious rats

The role of endothelin receptor subtypes, i.e., ETA and ETB receptors, in the behavioral effects of the intracerebroventricular (ICV) administration of endothelin-l were examined in conscious rats. ICV administration of endothelin-l (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-l (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 ETA receptor antagonist, but not of BQ788 (15 nmol/rat, ICV), a specific endothelin ETB 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-l, which has affinity for both endothelin ETA and ETB receptors, most likely acts on central ETA receptors to evoke barrel rolling and other convulsive behaviors. In addition, activation of central ETB 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. (C) 1999 Elsevier Science Inc.