Differential Effects of Cocaine-Induced Seizures and Lethality on M1-Like Muscarinic and Dopaminergic D1- and D2-Like Binding Receptors in Mice Brain

Summary This work was designed to study the changes produced by cocaine-induced seizures and lethality on dopaminergic D₁- and D₂-like receptors, muscarinic M₁-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 ³H]-N-methylscopolamine, ³H]-NMS (in the presence of carbachol), ³H]-SCH 23390 and ³H]-spiroperidol (in presence of mianserin), for muscarinic (M₁-like), D₁- and D₂-like receptors, respectively. Brain acetylcholinesterase (AChE) activity was also determined in these brain areas. Cocaine-induced SE decreased ³H]-SCH 23390 binding in both ST and PFC areas. A decrease in ³H]-NMS binding and an increase in ³H]-spiroperidol binding in PFC was also observed. Cocaine-induced lethality increased ³H]-spiroperidol binding in both areas and decreased ³H]-NMS binding only in PFC, while no difference was seen in ³H]-SCH 23390 binding. Neither SE, nor lethality altered ³H]-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.