SELECTIVELY BRED LINES OF RATS DIFFER IN SOCIAL-INTERACTION AND HIPPOCAMPAL 5-HT1A RECEPTOR FUNCTION - A LINK BETWEEN ANXIETY AND DEPRESSION

Selective breeding for high and low sensitivity to the hypothermic res ponse of the 5-HT1A receptor agonist 8-OH-DPAT has established two lin es (HDS and LDS, respectively) whose behavior differs in a model of de pression, but not in the elevated plus-maze test of anxiety. The lines also differed in postsynaptic, but not presynaptic, 5-HT1A receptors. Based on previous evidence that postsynaptic 5-HT1A receptors mediate anxiogenic effects in the social interaction test of anxiety, but not the elevated plus-maze, we investigated possible differences between the lines in these two tests. The HDS line had a consistently lower le vel of social interaction compared with the LDS line, but no differenc es were found on any of the measures of the anxiety on trials 1 or 2 i n the elevated plus-maze. To determine whether the line differences in anxiety were mediated by different hippocampal 5-HT1A receptor functi on, 8-OH-DPAT (50 and 100 ng) was applied bilaterally to the dorsal hi ppocampus. This elicited anxiogenic effects in the LDS line, as has be en previously reported in other rat strains, but there was no response in the HDS line, thus demonstrating an abnormal 5-HT1A receptor funct ion in the hippocampus. The 5-HT1A receptor antagonist WAY100635 (200 ng) was administered to the dorsal hippocampus to test for possible di fferences between the lines in 5-HT tone. There were no significant ch anges in social interaction in either the HDS or LDS rats, indicating that the different level of anxiety between lines is not due to differ ences in hippocampal 5-HT tone. It is proposed that the HDS line may p rove a useful model of a type of high trait anxiety linked to a suscep tibility to depression. (C) 1998 Elsevier Science Inc.