title: 8-OHDPAT-induced disruption of prepulse inhibition in rats is attenuated by prolonged corticosterone treatment.
abstract: The present study investigated the impact of acute and repeated administrations of corticosterone (10 mg/kg, twice daily, for 7 days) on serotonin (5-HT)(1A) receptor function, density and expression. The effect on 5-HT(1A) receptor function was assayed in rats by assessing the corticosterone-induced modulation of disruption of prepulse inhibition (PPI) of acoustic startle response induced by 8-OHDPAT, a 5-HT(1A) receptor agonist. Our experiments revealed that repeated but not acute treatment with corticosterone attenuated the 8-OHDPAT-evoked disruption of PPI without having any effect on PPI or startle amplitude alone. Chronic corticosterone treatment modulated also the neuronal activity of serotonergic pathways in the brain decreasing the level of 5-HIAA in the raphe nuclei and increasing both 5-HT and 5-HIAA levels in the hippocampus. Nevertheless, the effects of 8-OHDPAT on 5-HT metabolism were not changed by corticosterone. However, 5-HT(1A) receptor binding in the ventral hippocampus and entorhinal cortex but not in the raphe nuclei was decreased after chronic corticosterone treatment. It is concluded that chronically elevated corticosterone level is capable of inducing functional desensitization of 5-HT(1A) receptors which is paralleled by decreases in the 5-HT(1A) receptor binding in the ventral hippocampus and entorhinal cortex, the brain structures shown to be engaged in the regulation of PPI. Alterations in 5-HT(1A) receptors may be one of important mechanisms by which glucocorticoids/stress influence various psychiatric conditions.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. czyrak@if-pan.krakow.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Czyrak
authors.forename: Marzena
authors.initials: M
authors.lastname: Maćkowiak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chocyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Fijał
authors.forename: Anna
authors.initials: A
authors.lastname: Gadek-Michalska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wedzony
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000009:adverse effects*; D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001345:Autoradiography; D001665:Binding Sites; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D017403:In Situ Hybridization; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D013216:Reflex, Startle / Q000187:drug effects*; D012701:Serotonin / Q000097:blood; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D010879:Piperazines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone