Lewis and Fisher 344 strain differences in alpha2-adrenoceptors and tyrosine hydroxylase expression.

Abstract

Lewis and Fischer 344 (F344) rats differ in their pharmacological responses to a variety of drugs such as opioids, which has been partially attributed to differences in the endogenous opioid tone. Since opioid and a2-adrenergic mechanisms closely interact in nociception and substance abuse, a comparative study of the endogenous a2-adrenergic system in both inbred strains is of interest. Alpha-2 adrenoceptor subtypes and tyrosine hydroxylase, the rate-limiting enzyme of the catecholamine biosynthesis, were studied by Taqman RT-PCR analysis of gene expression in four brain areas of F344 and Lewis rats: hypothalamus, hippocampus, striatum and cortex. No differences were found in the mRNA levels of a2Aand a2C-adrenoceptors in any of the areas examined, however F344 rats exhibited lower levels of a2B-adrenoceptor transcripts in the hippocampus and higher levels in the hypothalamus. Tyrosine hydroxylase gene expression was found to be higher in hippocampus and striatum of F344 rats compared to Lewis, and a consistent 2-fold increase of the protein levels was detected by Western blots only in the case of the hippocampus. These results together with previous studies strongly suggest that the hippocampal noradrenergic activity of Lewis and F344 rats could be involved in their different responses to pain, stress and drug addiction.