Pilocarpine-induced seizures in adult rats: monoamine content and muscarinic and dopaminergic receptor changes in the striatum.
High doses of the muscarinic cholinergic agonist pilocarpine are a useful model for investigation of the essential mechanisms for seizure generation and spread in rodents. Pilocarpine (400 mg/kg; subcutaneously) was administered in 2-month-old female rats, and the content of striatum monoamines and (M(1)+M(2)) muscarinic and D(2) dopaminergic receptors was measured in the acute period. All treated animals showed peripheral cholinergic signs, stereotyped and clonic movements, tremors, seizures and the percentage mortality was approximately 63%. High performance liquid chromatography determinations, performed 24 h later, showed a decrease of striatal levels of dopamine, dihydroxyphenylacetic acid, 4-hydroxy-3-methoxy-phenylacetic acid and 5-hydroxytryptamine. Pilocarpine treatment induced downregulation of (M(1)+M(2)) muscarinic receptors and reduced the dissociation constants of (M(1)+M(2)) muscarinic and D(2) dopaminergic receptors, suggesting that these systems exert opposite effects on the regulation of convulsive activity. These and other important neurochemical changes found in the course of establishment of an epileptic focus can be observed after status epilepticus induced by pilocarpine.
Freitas
Rivelilson Mendes
RM
Department of Physiology and Pharmacology, Laboratory of Neuropharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Brazil.
Bezerra Felipe
Cícero F
CF
Nascimento
Viviane S
VS
Oliveira
Aline A
AA
Viana
Glauce S B
GS
Fonteles
Marta Maria de F
MM
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007279:Injections, Subcutaneous; D018721:Muscarinic Agonists; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality; D015996:Survival Rate
D015306:Biogenic Monoamines; D018721:Muscarinic Agonists; D011954:Receptors, Dopamine; D011976:Receptors, Muscarinic; D010862:Pilocarpine