Cocaine decreases the expression of PSA-NCAM protein and attenuates long-term potentiation via glucocorticoid receptors in the rat dentate gyrus

• Published in: The European journal of neuroscience 2008-06, Vol.27 (11), p.2928-2937
• Main Authors: Maćkowiak, Marzena, Grzegorzewska, Małgorzata, Budziszewska, Bogusława, Chocyk, Agnieszka, Hess, Grzegorz, Wędzony, Krzysztof
• Format: Article
• Language: English
• Subjects: Animals; Bromodeoxyuridine; Cell Count; Cell Proliferation - drug effects; Cocaine - pharmacology; Cocaine-Related Disorders - metabolism; Cocaine-Related Disorders - physiopathology; Corticosterone - antagonists & inhibitors; Corticosterone - blood; Dentate Gyrus - drug effects; Dentate Gyrus - metabolism; Dopamine Uptake Inhibitors - pharmacology; Down-Regulation - drug effects; Down-Regulation - physiology; drugs of abuse; hippocampus; Ki-67 Antigen - metabolism; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Memory - drug effects; Memory - physiology; Memory Disorders - chemically induced; Memory Disorders - metabolism; Memory Disorders - physiopathology; Metyrapone - analogs & derivatives; Metyrapone - pharmacology; Mifepristone - pharmacology; Mineralocorticoid Receptor Antagonists; mineralocorticoid receptors; neural cell adhesion molecule; Neural Cell Adhesion Molecule L1 - metabolism; Neurons - drug effects; Neurons - metabolism; Rats; Rats, Wistar; Receptors, Glucocorticoid - agonists; Receptors, Glucocorticoid - antagonists & inhibitors; Receptors, Glucocorticoid - metabolism; Receptors, Mineralocorticoid - metabolism; Sialic Acids - metabolism; Spironolactone - pharmacology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.1460-9568.2008.06255.x

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.