Decreased 5-HT1A and increased 5-HT2A receptor binding after chronic corticosterone associated with a behavioural indication of depression but not anxiety.
The effects of chronic corticosterone treatment (100 mg pellet implanted for 1 week) were assessed in animal tests of anxiety, exploration and motor activity, and changes in binding to 5-HT1A and 5-HT2A receptors, and the 5-HT transporter, were measured. At the end of the week's treatment, the corticosterone concentration was significantly elevated and there were significant decreases in adrenal, thymus and body weights. However, there were no changes in the measures of anxiety in the social interaction test or on trials 1 and 2 of the elevated plus-maze. Also supporting a dissociation between anxiety and elevated corticosterone concentrations are previous findings that benzodiazepine withdrawal causes increased anxiety but no change in corticosteroid concentrations. Therefore these two situations provide a double dissociation between anxiety and elevated corticosteroids. Decreased 5-HT1A receptor binding in the dentate gyrus and increased 5-HT2A receptor binding in the parietal cortex was found following chronic corticosterone treatment. This reciprocal relationship between 5-HT1A and 5-HT2A receptors has been proposed to be important in mediating depression. The significant decreases in motor activity observed in all the test situations would be compatible with this proposal. Thus the constellation of behavioural and biochemical changes detected after chronic corticosterone treatment is more pertinent to depression than anxiety. One week after removal of the pellets, the behavioural and neurochemical changes had disappeared and the only differences to remain were decreased adrenal, thymus and body weights in the animals that had been treated chronically with corticosterone.
Fernandes
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Psychopharmacology Research Unit, UMDS Division of Pharmacology, Guy's Hospital, London, UK.
McKittrick
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File
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McEwen
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BS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology*; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000494:pharmacology*; D003863:Depression / Q000523:psychology*; D005106:Exploratory Behavior / Q000187:drug effects; D007398:Interpersonal Relations; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D011985:Receptors, Serotonin; D003345:Corticosterone