title: Differential effects of cocaine-induced seizures and lethality on M(1)-like muscarinic and dopaminergic D (1)- and D (2)-like binding receptors in mice brain.
abstract: This work was designed to study the changes produced by cocaine-induced seizures and lethality on dopaminergic D(1)- and D(2)-like receptors, muscarinic M(1)-like binding sites, as well as acetylcholinesterase activity in mice prefrontal cortex (PFC) and striatum (ST). Binding assays were performed in brain homogenates from the PFC and ST and ligands used were [(3)H]-N-methylscopolamine, [(3)H]-NMS (in the presence of carbachol), [(3)H]-SCH 23390 and [(3)H]-spiroperidol (in presence of mianserin), for muscarinic (M(1)-like), D(1)- and D(2)-like receptors, respectively. Brain acetylcholinesterase (AChE) activity was also determined in these brain areas. Cocaine-induced SE decreased [(3)H]-SCH 23390 binding in both ST and PFC areas. A decrease in [(3)H]-NMS binding and an increase in [(3)H]-spiroperidol binding in PFC was also observed. Cocaine-induced lethality increased [(3)H]-spiroperidol binding in both areas and decreased [(3)H]-NMS binding only in PFC, while no difference was seen in [(3)H]-SCH 23390 binding. Neither SE, nor lethality altered [(3)H]-NMS binding in ST. AChE activity increased after SE in ST while after death the increase occurred in both PFC and ST. In conclusion, cocaine-induced SE and lethality produces differential changes in brain cholinergic and dopaminergic receptors, depending on the brain area studied suggesting an extensive and complex involvement of these with cocaine toxicity in central nervous system.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. daniellesm2000@yahoo.com
authors.forename: Danielle
authors.initials: D
authors.lastname: Silveira Macêdo
authors.forename: Silvânia Maria
authors.initials: SM
authors.lastname: Mendes Vasconcelos
authors.forename: Manoel
authors.initials: M
authors.lastname: Andrade-Neto
authors.forename: Marta Maria
authors.initials: MM
authors.lastname: França Fonteles
authors.forename: Lissiana Magna
authors.initials: LM
authors.lastname: Vasconcelos Aguiar
authors.forename: Glauce Socorro
authors.initials: GS
authors.lastname: Barros Viana
authors.forename: Francisca Cléa
authors.initials: FC
authors.lastname: Florençode Sousa
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology / Q000633:toxicity; D018492:Dopamine Antagonists / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D008297:Male; D051379:Mice; D019832:N-Methylscopolamine / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010276:Parasympatholytics; D043643:Receptor, Muscarinic M1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D000110:Acetylcholinesterase; D003042:Cocaine; D019832:N-Methylscopolamine