title: Cerebral ischemia-induced difference in sensitivity to depression and potential therapeutics in rats.
abstract: The 'vascular depression' hypothesis has recently attracted significant research attention, although the causal relationship between vascular-related injuries and depression has not been established. Here, we show that one episode of cerebral ischemia was sufficient to greatly increase the sensitivity of rats to potentially depressogenic events, evaluated at below-threshold intensities in the open space swim test. The induced 'ischemic depression' was lasting and sensitive to an acute administration of brain-derived neurotrophic factor or bryostatin-1, a relatively selective activator of protein kinase Cε, during the induction phase. Chronic treatment with bryostatin-1 (5 weeks) after the induction of depressive behavior reversed the depressive immobility and produced a lasting therapeutic effect, which remained effective 3 weeks after discontinuation of the treatment. Similar treatment with alaproclate, a selective serotonin reuptake inhibitor, in contrast, produced temporary relief from the depressive symptoms, with the therapeutic effect disappearing soon after the end of the treatment. The results strongly suggest that cerebral ischemia has a direct role in shaping the sensitivity of an individual to depressogenic events and that bryostatin-1-like agents may be developed as therapeutics for treating ischemic depression in humans.
authors.affiliation: Blanchette Rockefeller Neurosciences Institute, Rockville, MD 20850, USA. mksun@brni-jhu.org
authors.forename: Miao-Kun
authors.initials: MK
authors.lastname: Sun
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Alkon
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage; D054713:Bryostatins / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005518:Food Preferences / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D020287:In Situ Nick-End Labeling; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000008:administration & dosage; D013549:Sweetening Agents / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000276:Adjuvants, Immunologic; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D054713:Bryostatins; D013549:Sweetening Agents; C046785:bryostatin 1; D013395:Sucrose