Altered dendritic spine density in animal models of depression and in response to antidepressant treatment.
Olfactory bulbectomy, neonatal clomipramine administration, and maternal deprivation have been employed as animal models of depression. Each model is unique with respect to the experimental manipulations required to produce "depressive" signs, expression and duration of these signs, and response to antidepressant treatments. Dendritic spines represent a possible anatomical substrate for the enduring changes seen with depression and we have previously shown that chronic antidepressant drug exposure alters the density of hippocampal dendritic spines in an enduring fashion. The purpose of the present study was to determine whether persistent alteration of hippocampal spine density is a common element in each of these different models of depression and whether such alterations could be reversed with chronic antidepressant treatment. The results show that olfactory bulbectomy reduced spine density in CA1, CA3, and dentate gyrus compared to sham-operated controls. Chronic treatment with amitriptyline, a tricyclic antidepressant, reversed the bulbectomy- induced reduction in dendritic spine density in CA1, CA3, and dentate gyrus, whereas treatment with mianserin, an atypical antidepressant, reversed this reduction only in dentate gyrus. On the other hand, neither neonatal clomipramine administration nor maternal deprivation affected hippocampal dendritic spine density. Repeated neonatal handling, however, as a control or as part of the maternal deprivation procedure, elevated spine density in dentate gyrus. These data suggest that long-lasting alterations in hippocampal dendritic spine density contribute to the neural mechanism underlying the olfactory bulbectomy model of depression, but not the neonatal clomipramine or maternal deprivation models.
Norrholm
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SD
Program in Neuroscience, Department of Psychology, Florida State University, Tallahassee, Florida 32306-4340, USA.
Ouimet
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CC
D000818:Animals; D000831:Animals, Newborn; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D008426:Maternal Deprivation; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009830:Olfactory Bulb / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine