Effects of clonidine and yohimbine on the levels of bax, Bcl-XL, and caspase-3 mRNAs in the brain of neonatal rats

Abstract

Administration of clonidine, an agonist of alpha2-adrenoceptors at a dose of 0.4 mg/kg to a 3-day-old rat pups decreased the amount of proapoptotic protein Bax mRNA in the hippocampus and increased the content of antiapoptotic protein Bcl-XL mRNA in the brainstem 120 h after treatment. Administration of yohimbine, an antagonist of alpha2-adrenoceptors, at a dose of 2 mg/kg increased the level of Bcl-XL mRNA in the hippocampus at the same time point. These effects were specific for each drug. However, both these substances decreased the amount of mRNAs of Bax and the key executive apoptotic protease, caspase-3, in the cerebral cortex 24 and 120 h after treatment, respectively. Similar effects of clonidine and yohimbine suggest that the effect of the antagonist of alpha2-adrenoceptors was possibly mediated by endogenous norepinephrine released in response to the antagonist. These results may explain the neuroprotective features of agonists and antagonists of alpha2-adrenoceptors, which have been previously reported.