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 response of the 5-HT1A receptor agonist 8-OH-DPAT has established two lines (HDS and LDS, respectively) whose behavior differs in a model of depression, 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 level of social interaction compared with the LDS line, but no differences were found on any of the measures of the anxiety on trials 1 or 2 in the elevated plus-maze. To determine whether the line differences in anxiety were mediated by different hippocampal 5-HT1A receptor function, 8-OH-DPAT (50 and 100 ng) was applied bilaterally to the dorsal hippocampus. This elicited anxiogenic effects in the LDS line, as has been previously reported in other rat strains, but there was no response in the HDS line, thus demonstrating an abnormal 5-HT1A receptor function in the hippocampus. The 5-HT1A receptor antagonist WAY100635 (200 ng) was administered to the dorsal hippocampus to test for possible differences between the lines in 5-HT tone. There were no significant changes in social interaction in either the HDS or LDS rats, indicating that the different level of anxiety between lines is not due to differences in hippocampal 5-HT tone. It is proposed that the HDS line may prove a useful model of a type of high trait anxiety linked to a susceptibility to depression.
Gonzalez
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Psychopharmacology Research Unit, UMDS, Guy's Hospital, London, UK.
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Overstreet
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism*; D003866:Depressive Disorder / Q000235:genetics* / Q000378:metabolism*; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D007398:Interpersonal Relations; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013045:Species Specificity; D013238:Stereotaxic Techniques
D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin