title: Cocaine decreases the expression of PSA-NCAM protein and attenuates long-term potentiation via glucocorticoid receptors in the rat dentate gyrus.
abstract: The present study investigated a potential role for glucocorticoid (GR) and mineralocorticoid (MR) receptors in the detrimental effects of single cocaine (COC) administration on both the number of polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neurons and the induction of long-term potentiation (LTP) in the rat dentate gyrus (DG). The effects of COC (15 mg/kg i.p.) on the number of PSA-NCAM-positive neurons and the induction of LTP observed 2 days after COC administration were abolished either by depleting circulating corticosterone after administration of metyrapone (100 mg/kg s.c. given 3 h before COC) or by pharmacologically blocking GRs using mifepristone (RU 38486, 10 mg/kg s.c. given 1 h before COC). Administration of the MR blocker spironolactone (50 mg/kg s.c. given 1 h before COC) did not alter the effects of COC on the number of PSA-NCAM-positive neurons or LTP induction. Results have also shown that COC does not change the rate of cell proliferation, as measured by the presence of Ki-67 and the incorporation of bromodeoxyuridine (100 mg/kg i.p. given 2 h after COC) into the newly born cells in the DG 2 days after COC administration. Finally, we observed that GRs colocalized with some, but not all, PSA-NCAM-positive neurons, whereas MRs showed no colocalization with neurons positive for PSA-NCAM in the DG. These data indicate that a single dose of COC may arrest hippocampal susceptibility to plastic changes and lead to functional impairments through the alteration of hippocampal structure and the formation of memory traces.
authors.affiliation: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. mackow@if-pan.krakow.pl
authors.forename: Marzena
authors.initials: M
authors.lastname: Maćkowiak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Grzegorzewska
authors.forename: Bogusława
authors.initials: B
authors.lastname: Budziszewska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Chocyk
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Hess
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Wedzony
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003345:Corticosterone / Q000037:antagonists & inhibitors / Q000097:blood; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019394:Ki-67 Antigen / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008797:Metyrapone / Q000031:analogs & derivatives / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D018765:Dopamine Uptake Inhibitors; D019394:Ki-67 Antigen; D000451:Mineralocorticoid Receptor Antagonists; D039842:Neural Cell Adhesion Molecule L1; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; C002196:metyrapol; D013148:Spironolactone; D015735:Mifepristone; D001973:Bromodeoxyuridine; D003042:Cocaine; D003345:Corticosterone; D008797:Metyrapone