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Divergent effects of putative anxiolytics on stress‐induced Fos expression in the mesoprefrontal system of the rat
Author(s) -
Morrow Bret A.,
Elsworth John D.,
Lee Edward J.K.,
Roth Robert H.
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(200005)36:2<143::aid-syn7>3.0.co;2-h
Subject(s) - ventral tegmental area , infralimbic cortex , guanfacine , dopaminergic , chemistry , agonist , prefrontal cortex , partial agonist , neuroscience , dopamine , endocrinology , medicine , psychology , biology , receptor , biochemistry , cognition , clonidine
Previously, we reported that R(+)HA‐966, a weak partial agonist for the glycine/NMDA receptor, and guanfacine, a noradrenergic α2 agonist, have anxiolytic‐like actions on the biochemical activation of the mesoprefrontal dopamine neurons and fear‐induced behaviors. Here, we examined these two putative anxiolytic agents, both with primary actions independent of GABAergic systems, for their ability to alter stress‐induced Fos‐like immunoreactivity in the mesoprefrontal cortex and in tyrosine hydroxylase‐stained, presumed dopaminergic, neurons in the ventral tegmental area. The benzodiazepine agonist, lorazepam, and partial agonist, bretazenil, were also tested in this footshock paradigm [10 × 0.5 sec, 0.8 mA paired with a 5‐sec tone]. In saline‐treated rats, footshock resulted in an increase in Fos‐li in the prelimbic and infralimbic cortices and tyrosine hydroxylase‐labeled cells in the ventral tegmental area. Treatment with lorazepam or bretazenil prevented the stress‐induced activation in Fos‐li nuclei in all regions of the medial prefrontal cortex and in dopaminergic neurons in the ventral tegmental area. In contrast, the actions of the novel anxiolytic‐like agents on stress‐induced Fos‐li were different than those observed with benzodiazepine agonists. Both putative anxiolytics, R(+)HA‐966 and guanfacine, did not reduce, but significantly enhanced the stress‐induced Fos‐li in the prelimbic region of the medial prefrontal cortex. Additionally, treatment with R(+)HA‐966 completely blocked, while guanfacine attenuated, the stress‐induced increase in the number of Fos‐li, TH‐li cells in the ventral tegmental area. These results indicate that the putative anxiolytics, R(+)HA‐966 and guanfacine, have actions on the stress‐sensitive mesoprefrontal system which appear distinct from those of traditional anxiolytics. Synapse 36:143–154, 2000. © 2000 Wiley‐Liss, Inc.