title: 5-HT1A receptors mediate detrimental effects of cocaine on long-term potentiation and expression of polysialylated neural cell adhesion molecule protein in rat dentate gyrus.
abstract: The present study investigated the involvement of 5-HT(1A) receptors in the inhibitory effect of single administration of cocaine (COC, 15 mg/kg i.p.) on the induction of long-term potentiation (LTP) in slices of rat dentate gyrus (DG), prepared 30 min and 2 days after COC administration. These effects of COC were blocked by an antagonist of 5-HT(1A) receptors, WAY 100635 (0.4 mg/kg i.p.), which had been administered 20 min before COC. The detrimental effect of COC on LTP in slices prepared 30 min after COC administration could be prevented by blocking glucocorticoid receptors (GRs) using mifepristone (RU 38486, 10 mg/kg s.c. given 1 h before COC), similar as in slices obtained 2 days after COC as reported previously [Maćkowiak et al. (2008) Eur J Neurosci 27:2928-2937]. After a single administration of an agonist of 5-HT(1A) receptors, 8-OH-DPAT, (0.5 mg/kg i.p.), the level of LTP in slices prepared 2 days later was significantly decreased resembling the effect of COC. This effect of 8-OH-DPAT was antagonized by WAY 100635 (0.4 mg/kg i.p.), administered 20 min before 8-OH-DPAT and by RU 38486, given 1 h before 8-OH-DPAT. COC-induced inhibition of LTP could be blocked by the inhibitor of mitogen-activated protein kinase kinase 1/2 (MEK1/2), SL 327 (50 mg/kg i.p.), administered 1 h before COC, but not by the inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), LY 294002 (80 mg/kg i.p.). COC-induced reduction in the number of polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neurons in rat dentate gyrus could also be prevented by WAY 100635, given 20 min before COC. These data indicate that the indirect 5-HT(1A) receptor activation by a single COC administration and subsequent stimulation of extracellular signal-regulated kinases (ERK 1/2) signaling pathway result in a decrease of the potential for long-term increase in synaptic efficacy in rat DG lasting at least two but less than 7 days, most likely via activation of the hypothalamic-pituitary-adrenal (HPA) axis.
authors.affiliation: Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Grzegorzewska
authors.forename: M
authors.initials: M
authors.lastname: Maćkowiak
authors.forename: K
authors.initials: K
authors.lastname: Wedzony
authors.forename: G
authors.initials: G
authors.lastname: Hess
mesh_terms: D000818:Animals; D002452:Cell Count; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012794:Sialic Acids / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D039842:Neural Cell Adhesion Molecule L1; D011965:Receptors, Glucocorticoid; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D044282:Receptor, Serotonin, 5-HT1A; D015735:Mifepristone; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D003042:Cocaine