Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress

Both repeated stress and corticosterone administration induce remodeling of apical dendrites of hippocampal CA3 pyramidal neurons. Circulating glucoco rticoids are involved in the mechanism that produces atrophy, along with ex citatory amino acids and serotonin (5-hydroxytryptamine, 5-HT). We used 5-H T-related antidepressants and a benzodiazepine in order to explore indirect ly the role of serotonin and GABA(A)-benzodiazepine receptors in the stress -induced structural changes visualized by the Golgi impregnation of the rat hippocampus. The 5-HT reuptake enhancer (+/-)-tianeptine prevented the den dritic atrophy caused by repeated restraint stress in a non-stereoselective fashion and two 5-HT reuptake antagonists, fluoxetine and fluvoxamine, fai led to block dendritic atrophy. Tianeptine also functions as a therapeutic tool since it reversed the already established hippocampal atrophy caused b y treatment with corticosterone for 3 weeks. Finally, the benzodiazepine ag onist adinazolam was effective in preventing the stress-induced dendritic a trophy. These findings suggest that the synaptic availability of 5-HT is in volved in the mechanism leading to stress-induced dendritic remodeling and supports the idea that the hippocampal inhibitory GABAergic tone may play a regulatory role. (C) 1999 Elsevier Science B.V. All rights reserved.