title: Only repeated administration of the serotonergic agonist 8-OH-DPAT improves place learning of rats subjected to fimbria-fornix transection.
abstract: Serotonergic agonists may act neuroprotectively against brain injury. This study addressed the therapeutic potential of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT), a selective 5-HT1A/7 receptor agonist, after mechanical brain injury, and evaluated its effects in terms of acquisition of an allocentric place learning task in a water maze. Rats were divided into 6 experimental groups, three of which were subjected to bilateral transection of fimbria-fornix (FF), while three groups were given control surgery (Sham). After surgery, within both the lesioned, and sham-operated animals, respectively, one group was administered a single dose of saline, one group was given a single dose (0.5 mg/kg/b.w.) of 8-OH-DPAT, and one group was treated with daily administration of 8-OH-DPAT (0.5 mg/kg/b.w.) for eight days. The acquisition of the water maze based place learning task started on the 8th day post-surgery and continued for 20 days. The results show that the lesioned group subjected to repeated administration of 8-OH-DPAT demonstrated a significantly improved acquisition of the place learning task compared to the vehicle injected lesion group. In contrast, the lesioned group treated with a single administration displayed impaired performance compared to the baseline lesion group. There were no significant effects of the 8-OH-DPAT administration in the sham control groups. We conclude that only the repeated stimulation of the 5-HT1A/7 system was associated with beneficial, recovery enhancing effects.
authors.affiliation: The Unit for Cognitive Neuroscience, Department of Psychology, University of Copenhagen, Denmark.
authors.forename: Hana
authors.initials: H
authors.lastname: Malá
authors.forename: Kasper
authors.initials: K
authors.lastname: Arnberg
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.forename: Signe Kjær
authors.initials: SK
authors.lastname: Nedergaard
authors.forename: Jacqlyn
authors.initials: J
authors.lastname: Witmer
authors.forename: Jesper
authors.initials: J
authors.lastname: Mogensen
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D020712:Fornix, Brain / Q000601:surgery*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin